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Bai Y, Zhang H, Lin Z, Huang S, Xie F, Gao S, Wong CCL, Wu Y, Wang X, Zhao H, Zhang Y. Lung cancer associated transcript 1 binds heat shock protein 90 to promote growth of hepatocellular carcinoma. Cell Signal 2025; 129:111671. [PMID: 39971224 DOI: 10.1016/j.cellsig.2025.111671] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 01/08/2025] [Accepted: 02/14/2025] [Indexed: 02/21/2025]
Abstract
Hepatocellular carcinoma (HCC) is one of leading causes of cancer-related death and new approaches are urgently needed, given current dearth of therapies. Long non-coding RNAs (lncRNAs) have been linked to cancer formation and impact cell regulatory pathways. We have investigated molecular mechanisms of action of "lung cancer associated transcript 1" (LUCAT1, a lncRNA) in HCC and studied the potential role of targeting these. We analyzed expression levels of LUCAT1 in TCGA dataset and another 148 HCC patients in Peking Union Medical College Hospital (PUMCH). Expression analysis using TCGA database and patient cohort revealed LUCAT1 to be upregulated in HCC. LUCAT1 levels were closely associated with clinical prognosis. Subcellular localization patterns of LUCAT1 in HCC tissues and cells were identified by RNAscope. Engineered antisense oligonucleotides (ASOs) targeting LUCAT1 were used to test anti-tumor effectiveness using in vitro and in vivo models. CHIRP-MS and RNA pull-down assays were conducted to demonstrate the mechanism of action of LUCAT1.LUCAT1 expression facilitated nuclear accumulation of HSP90. This interaction evoked persistent phosphorylation and constitutive activation of signal transducer and activator of transcription 3 (STAT3), potentially driving HCC growth and metastases. These tumor-promoting effects were substantively diminished using ASOs against LUCAT1, both in vitro and in vivo. LUCAT1 selectively boosts oncogenic property of HSP90 in driving STAT3 activation, which can be effectively and precisely inhibited by designer ASOs. We propose novel potential therapeutic avenues that are selective, cost-effective and seemingly nontoxic.
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Affiliation(s)
- Yi Bai
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing 100730, China; Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Tianjin 300192, China
| | - Haohai Zhang
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing 100730, China; Division of Gastroenterology, Department of Medicine & Department of Anesthesia, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
| | - Zijie Lin
- Tianjin Medical University, Tianjin 300070, China
| | - Shan Huang
- Beijing Institute of Infectious Diseases, Beijing 100015, China; The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease of Ministry of Education, Department of Cell Biology, Tianjin Medical University, Tianjin 300070, China; Institute of Infectious Diseases, National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
| | - Fucun Xie
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing 100730, China; Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing 100021, China; State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing 100021, China
| | - Shuaixin Gao
- Department of Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), 100730 Beijing, China; Tsinghua University-Peking University Joint Center for Life Sciences, Tsinghua University, 100084 Beijing, China
| | - Catherine C L Wong
- Department of Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), 100730 Beijing, China; Tsinghua University-Peking University Joint Center for Life Sciences, Tsinghua University, 100084 Beijing, China.
| | - Yan Wu
- Division of Gastroenterology, Department of Medicine & Department of Anesthesia, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Xi Wang
- Beijing Institute of Infectious Diseases, Beijing 100015, China; Institute of Infectious Diseases, National Center for Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China.
| | - Haitao Zhao
- Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing 100730, China.
| | - Yamin Zhang
- Department of Hepatobiliary Surgery, Tianjin First Central Hospital, Tianjin 300192, China.
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Zhang X, Li J, He J, Li Y, Sun D, Zhang W. Glutathion peroxidase 4 (GPX4) and Ribosomal Protein L40 (RPL40) participate in arsenic induced progression of renal cell carcinoma by regulating the NLRP3 mediated classic pyroptosis pathway. Int J Biol Macromol 2025; 310:143129. [PMID: 40239794 DOI: 10.1016/j.ijbiomac.2025.143129] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2025] [Revised: 04/08/2025] [Accepted: 04/11/2025] [Indexed: 04/18/2025]
Abstract
Epidemiological studies have demonstrated that long-term exposure to high‑arsenic water increases the risk of kidney cancer. Kidney dysfunction can lead to the accumulation of metabolic waste and chronic inflammation, with the latter being a significant factor in tumor development. Therefore, it is crucial to investigate how environmental arsenic exposure affects renal function and inflammation, as well as its potential influence on the progression of renal carcinoma. Additionally, pyroptosis plays an essential role in immune responses and the maintenance of cellular homeostasis. However, the role and mechanisms of pyroptosis in arsenic-induced kidney cancer progression remain unexplored. Our findings indicated that low-dose arsenic exposure reduces pyroptosis and promotes abnormal proliferation of renal tubular epithelial cells, while high-dose exposure enhances pyroptosis and damages renal tissue structure in mouse models. Mechanistically, in vitro studies confirmed that low-dose arsenic exposure promotes the progression of renal cell carcinoma by downregulating NLRP3 and inhibiting pyroptosis, whereas high-dose exposure has the opposite effect. Proteomics analysis identified GPX4 and RPL40 as key proteins mediating pyroptosis induced by low and high doses of arsenic, respectively. Furthermore, GPX4 and RPL40 were shown to regulate the malignant progression of renal cell carcinoma through their effects on NLRP3-mediated pyroptosis. This study reveals that arsenic exposure induces pyroptosis via NLRP3, leading to renal injury and influencing the malignant progression of renal cancer. Notably, GPX4 and RPL40 regulate this progression under low and high-dose arsenic exposure, respectively.
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Affiliation(s)
- Xiaodan Zhang
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University), Harbin 150081, China; Joint Key Laboratory of Endemic Diseases (Harbin Medical University Guizhou Medical University Xi'an Jiaotong University), Harbin 150081, China
| | - Jinyu Li
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University), Harbin 150081, China; Joint Key Laboratory of Endemic Diseases (Harbin Medical University Guizhou Medical University Xi'an Jiaotong University), Harbin 150081, China
| | - Jing He
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University), Harbin 150081, China; Joint Key Laboratory of Endemic Diseases (Harbin Medical University Guizhou Medical University Xi'an Jiaotong University), Harbin 150081, China
| | - Yuanyuan Li
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University), Harbin 150081, China; Joint Key Laboratory of Endemic Diseases (Harbin Medical University Guizhou Medical University Xi'an Jiaotong University), Harbin 150081, China
| | - Dianjun Sun
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University), Harbin 150081, China; Joint Key Laboratory of Endemic Diseases (Harbin Medical University Guizhou Medical University Xi'an Jiaotong University), Harbin 150081, China.
| | - Wei Zhang
- Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, China; NHC Key Laboratory of Etiology and Epidemiology (Harbin Medical University), Harbin 150081, China; Joint Key Laboratory of Endemic Diseases (Harbin Medical University Guizhou Medical University Xi'an Jiaotong University), Harbin 150081, China.
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ZHANG HENG, YANG XIAO, GUO YUJIN, ZHAO HAIBO, JIANG PEI, YU QINGQING. The regulatory role of lncRNA in tumor drug resistance: refracting light through a narrow aperture. Oncol Res 2025; 33:837-849. [PMID: 40191723 PMCID: PMC11964869 DOI: 10.32604/or.2024.053882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Accepted: 08/05/2024] [Indexed: 04/09/2025] Open
Abstract
As living conditions improve and diagnostic capabilities advance, the incidence of tumors has increased, with cancer becoming a leading cause of death worldwide. Surgery, chemotherapy, and radiotherapy are the most common treatments. Despite advances in treatment options, chemotherapy remains a routine first-line treatment for most tumors. Due to the continuous and extensive use of chemotherapy drugs, tumor resistance often develops, becoming a significant cause of treatment failure and poor prognosis. Recent research has increasingly focused on how long stranded non-coding RNAs (LncRNAs) influence the development of malignant tumors and drug resistance by regulating gene expression and other biological mechanisms during cell growth. Studies have demonstrated that variations in lncRNA expression levels, influenced by both interpatient variability and intratumoral genetic and epigenetic differences, are closely linked to tumor drug resistance. Therefore, this review advocates using lncRNA as a framework to investigate the regulation of genes associated with drug resistance, proposing lncRNA-targeted therapeutic strategies to potentially increase the efficacy of chemotherapy, improve patient outcomes, and guide future research directions.
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Affiliation(s)
- HENG ZHANG
- Department of Laboratory, Shandong Daizhuang Hospital, Jining, 272051, China
| | - XIAO YANG
- Department of Anesthesiology, Affiliated Hospital of Jining Medical University, Jining, 272000, China
| | - YUJIN GUO
- Department of Clinical Pharmacy, Jining No.1 People’s Hospital, Jining, 272002, China
| | - HAIBO ZHAO
- Department of Oncology, Jining No.1 People’s Hospital, Jining, 272002, China
| | - PEI JIANG
- Translational Pharmaceutical Laboratory, Jining No.1 People’s Hospital, Jining, 272002, China
| | - QING-QING YU
- Department of Clinical Pharmacy, Jining No.1 People’s Hospital, Jining, 272002, China
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Shang J, Chen Y, Jiang Q, Li W, Lu M, Zhou J, Lin L, Xing J, Zhang M, Zhao S, Lu J, Shi X, Liu Y, Zhu X. The long noncoding RNA LUCAT1 regulates endometrial receptivity via the miR-495-3p/S100P axis. Commun Biol 2025; 8:318. [PMID: 40011637 DOI: 10.1038/s42003-025-07718-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Accepted: 02/11/2025] [Indexed: 02/28/2025] Open
Abstract
Recently, interest in investigating the effects of long noncoding RNAs (lncRNAs) on endometrial receptivity (ER) has increased within the field of assisted reproductive technology. Therefore, the objective of this study is to identify and analyze the role of the lncRNA LUCAT1 and to elucidate its specific mechanism in regulating ER. Hub genes associated with ER are identified via Weighted gene co-expression network analysis (WGCNA) in two datasets downloaded from the GEO database. These hub genes identified via WGCNA were subsequently validated. The combination of a dual-luciferase assay, qRT‒PCR, western blotting, and other techniques are used to investigate the molecular mechanism by which LUCAT1 regulates S100P. In this study, LUCAT1 expression is shown to significantly affect ER, and the depletion of LUCAT1 leads to impaired ER function. Additionally, LUCAT1 is shown to act as a molecular sponge for miR-495-3p, thereby modulating the expression of S100P. This modulation influences the proliferation, migration, and invasion capabilities of Ishikawa cells, as well as the adhesion of JAR cells to endometrial cells. Therefore, LUCAT1 can regulate ER via the miR-495-3p/S100P axis, which provides experimental evidence for the identification of innovative strategies aimed at enhancing endometrial receptivity.
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Affiliation(s)
- Junyu Shang
- Reproductive Medicine Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Department of Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Reproductive Sciences Institute, Jiangsu University, Zhenjiang, China
| | - Yumei Chen
- Department of Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- The Department of Gynecology, the Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
| | - Qianwen Jiang
- College of Pharmacy, Guangxi University, Nanning, China
| | - Wenxin Li
- Reproductive Medicine Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Department of Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Reproductive Sciences Institute, Jiangsu University, Zhenjiang, China
| | - Minjun Lu
- Reproductive Medicine Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Department of Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Reproductive Sciences Institute, Jiangsu University, Zhenjiang, China
| | - Jiamin Zhou
- Reproductive Medicine Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Department of Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Reproductive Sciences Institute, Jiangsu University, Zhenjiang, China
| | - Li Lin
- Reproductive Medicine Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Department of Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Reproductive Sciences Institute, Jiangsu University, Zhenjiang, China
| | - Jie Xing
- Reproductive Medicine Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Department of Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Reproductive Sciences Institute, Jiangsu University, Zhenjiang, China
| | - Mengxue Zhang
- Reproductive Medicine Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Department of Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Reproductive Sciences Institute, Jiangsu University, Zhenjiang, China
| | - Shijie Zhao
- Reproductive Medicine Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Department of Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Reproductive Sciences Institute, Jiangsu University, Zhenjiang, China
| | - Jingjing Lu
- Reproductive Medicine Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Department of Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Reproductive Sciences Institute, Jiangsu University, Zhenjiang, China
| | - Xuyan Shi
- Reproductive Medicine Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Department of Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Reproductive Sciences Institute, Jiangsu University, Zhenjiang, China
| | - Yueqin Liu
- Reproductive Medicine Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Department of Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China
- Reproductive Sciences Institute, Jiangsu University, Zhenjiang, China
| | - Xiaolan Zhu
- Reproductive Medicine Center, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China.
- Department of Central Laboratory, The Fourth Affiliated Hospital of Jiangsu University, Zhenjiang, China.
- Reproductive Sciences Institute, Jiangsu University, Zhenjiang, China.
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Gu X, Hu X, Zhang S, Zhang X, Wang Y, Li L. The diagnostic and prognostic significance of HOXC13-AS and its molecular regulatory mechanism in human cancer. Front Mol Biosci 2025; 12:1540048. [PMID: 39981436 PMCID: PMC11839424 DOI: 10.3389/fmolb.2025.1540048] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Accepted: 01/15/2025] [Indexed: 02/22/2025] Open
Abstract
HOXC13 antisense RNA (HOXC13-AS, also known as HOXC-AS5) is a long non-coding RNA that is expressed abnormally in various types of tumors and is closely related to clinical staging, clinical pathological features, and patient survival. HOXC13-AS is involved in the occurrence and development of tumors, affecting cell proliferation, migration, invasion, epithelial-mesenchymal transition, and tumor growth. This review summarizes the clinical significance of HOXC13-AS as a biomarker for human tumor diagnosis and prognosis and outlines the function and molecular regulation mechanism of HOXC13-AS in various types of cancer, including nasopharyngeal carcinoma, breast cancer, oral squamous cell carcinoma, glioma, and cervical cancer. Overall, this review emphasizes the potential of HOXC13-AS as a human tumor predictive biomarker and therapeutic target, paving the way for its clinical application.
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Affiliation(s)
- Xiaosi Gu
- Department of Immunology, School of Clinical and Basic Medical Sciences, Shandong First Medical University, Jinan, Shandong, China
| | - Xin Hu
- Department of Immunology, School of Clinical and Basic Medical Sciences, Shandong First Medical University, Jinan, Shandong, China
| | - Sijia Zhang
- Department of Immunology, School of Clinical and Basic Medical Sciences, Shandong First Medical University, Jinan, Shandong, China
| | - Xiaoyu Zhang
- Department of Immunology, School of Clinical and Basic Medical Sciences, Shandong First Medical University, Jinan, Shandong, China
| | - Yong Wang
- Shandong Provincial Engineering Research Center for Bacterial Oncolysis and Cell Treatment, Jinan, Shandong, China
| | - Lianlian Li
- Department of Immunology, School of Clinical and Basic Medical Sciences, Shandong First Medical University, Jinan, Shandong, China
- Laboratory of Metabolism and Gastrointestinal Tumor, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, China
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Chakraborty R, Dutta A, Mukhopadhyay R. TP53 mutations and MDM2 polymorphisms in breast and ovarian cancers: amelioration by drugs and natural compounds. Clin Transl Oncol 2025:10.1007/s12094-024-03841-6. [PMID: 39797946 DOI: 10.1007/s12094-024-03841-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2024] [Accepted: 12/24/2024] [Indexed: 01/13/2025]
Abstract
Globally, breast and ovarian cancers are major health concerns in women and account for significantly high cancer-related mortality rates. Dysregulations and mutations in genes like TP53, BRCA1/2, KRAS and PTEN increase susceptibility towards cancer. Here, we discuss the impact of mutations in the key regulatory gene, TP53 and polymorphisms in its negative regulator MDM2 which are reported to accelerate cancer progression. Missense mutations, null mutations, transversions, transitions, and point mutations occurring in the TP53 gene can cause an increase in metastatic activity. This review discusses mutations occurring in exon regions of TP53, polymorphisms in MDM2 and their interaction with large ribosomal subunit protein (RPL) leading to cancer development. We also highlight the potential of small molecules e.g. p53 activators like XI-011, Tenovin-1, and Nutlin-3a for the treatment of breast and ovarian cancers. The therapeutic efficacy of natural compounds in amelioration of these two types of cancers is also discussed.
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Affiliation(s)
- Rituraj Chakraborty
- Inflammation and Cancer Biology Laboratory, Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur, Assam, 784028, India
| | - Anupam Dutta
- Inflammation and Cancer Biology Laboratory, Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur, Assam, 784028, India
| | - Rupak Mukhopadhyay
- Inflammation and Cancer Biology Laboratory, Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur, Assam, 784028, India.
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Yang Y, Hong Y, Zhao K, Huang M, Li W, Zhang K, Zhao N. Spatial transcriptomics analysis identifies therapeutic targets in diffuse high-grade gliomas. Front Mol Neurosci 2024; 17:1466302. [PMID: 39530009 PMCID: PMC11552449 DOI: 10.3389/fnmol.2024.1466302] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 10/01/2024] [Indexed: 11/16/2024] Open
Abstract
Introduction Diffuse high-grade gliomas are the most common malignant adult neuroepithelial tumors in humans and a leading cause of cancer-related death worldwide. The advancement of high throughput transcriptome sequencing technology enables rapid and comprehensive acquisition of transcriptome data from target cells or tissues. This technology aids researchers in understanding and identifying critical therapeutic targets for the prognosis and treatment of diffuse high-grade glioma. Methods Spatial transcriptomics was conducted on two cases of isocitrate dehydrogenase (IDH) wild-type diffuse high-grade glioma (Glio-IDH-wt) and two cases of IDH-mutant diffuse high-grade glioma (Glio-IDH-mut). Gene set enrichment analysis and clustering analysis were employed to pinpoint differentially expressed genes (DEGs) involved in the progression of diffuse high-grade gliomas. The spatial distribution of DEGs in the spatially defined regions of human glioma tissues was overlaid in the t-distributed stochastic neighbor embedding (t-SNE) plots. Results We identified a total of 10,693 DEGs, with 5,677 upregulated and 5,016 downregulated, in spatially defined regions of diffuse high-grade gliomas. Specifically, SPP1, IGFBP2, CALD1, and TMSB4X exhibited high expression in carcinoma regions of both Glio-IDH-wt and Glio-IDH-mut, and 3 upregulated DEGs (SMOC1, APOE, and HIPK2) and 4 upregulated DEGs (PPP1CB, UBA52, S100A6, and CTSB) were only identified in tumor regions of Glio-IDH-wt and Glio-IDH-mut, respectively. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analyses revealed that upregulated DEGs were closely related to PI3K/Akt signaling pathway, virus infection, and cytokine-cytokine receptor interaction. Importantly, the expression of these DEGs was validated using GEPIA databases. Furthermore, the study identified spatial expression patterns of key regulatory genes, including those involved in protein post-translational modification and RNA binding protein-encoding genes, with spatially defined regions of diffuse high-grade glioma. Discussion Spatial transcriptome analysis is one of the breakthroughs in the field of medical biotechnology as this can map the analytes such as RNA information in their physical location in tissue sections. Our findings illuminate previously unexplored spatial expression profiles of key biomarkers in diffuse high-grade glioma, offering novel insight for the development of therapeutic strategies in glioma.
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Affiliation(s)
- Yongtao Yang
- Department of Neurosurgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Yingzhou Hong
- Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, China
| | - Kai Zhao
- Department of Neurosurgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Minhao Huang
- Department of Neurosurgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Wenhu Li
- Department of Neurosurgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Kui Zhang
- Department of Neurosurgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Ninghui Zhao
- Department of Neurosurgery, The Second Affiliated Hospital of Kunming Medical University, Kunming, China
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Baradaran-Bagherian S, Mehrab Mohseni M, Sharifi R, Amirinejad R, Shirvani-Farsani Z. The oxidative stress-associated long non-coding RNAs in pancreatic cancer. Adv Med Sci 2024; 69:231-237. [PMID: 38670228 DOI: 10.1016/j.advms.2024.04.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 12/18/2023] [Accepted: 04/23/2024] [Indexed: 04/28/2024]
Abstract
PURPOSE A lot of people are dying from pancreatic cancer (PC) annually. The early detection of this cancer is particularly challenging due to the fact that symptoms tend to appear in advanced stages. It has been suggested that oxidative stress may play a role in the development of PC. Several genes regulate this process, including long noncoding RNAs (lncRNAs). There is no comprehensive study on the expression pattern of lncRNAs related to oxidative stress in PC patients. In the present case-control study, we quantified levels of oxidative stress-associated lncRNAs in PC patients versus healthy controls. PATIENTS AND METHODS In the present study, we investigated the expression levels of lincRNA-p21, LUCAT, RMST, FOXD3-AS1, and MT1DP lncRNAs in the peripheral blood mononuclear cells (PBMCs) of 53 PC patients and 50 healthy controls. The association between lncRNA expression and clinical and pathological characteristics was also evaluated. RESULTS The expression of lincRNA-P21 and rhabdomyosarcoma 2-associated transcript (RMST) lncRNAs in PC patients has significantly decreased. Expression of lncRNA RMST was significantly higher in TNM stage III-IV patients in comparison to TNM stage I-II patients. In addition, a significant positive association was recognized between candidate lncRNA expression, and finally, the AUC values of the expression levels of lincRNA-p21 and RMST were 0.60 and 0.61, respectively. CONCLUSIONS Altogether, our study suggests a possible role of lincRNA-p21 and RMST lncRNAs in the etiology of PC pathobiology, and their biomarker role may be understood in future studies.
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Affiliation(s)
- Setayesh Baradaran-Bagherian
- Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | - Mahdieh Mehrab Mohseni
- Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran
| | - Roya Sharifi
- Department of Medical Laboratory Sciences, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
| | - Roya Amirinejad
- Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Zeinab Shirvani-Farsani
- Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran.
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Yu JM, Sun CQ, Xu HH, Jiang YL, Jiang XY, Ni SQ, Zhao TY, Liu LX. Navigating the labyrinth of long non-coding RNAs in colorectal cancer: From chemoresistance to autophagy. World J Gastrointest Oncol 2024; 16:3376-3381. [PMID: 39171173 PMCID: PMC11334040 DOI: 10.4251/wjgo.v16.i8.3376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2024] [Revised: 05/03/2024] [Accepted: 05/22/2024] [Indexed: 08/07/2024] Open
Abstract
Long non-coding RNAs (lncRNAs), with transcript lengths exceeding 200 nucleotides and little or no protein-coding capacity, have been found to impact colorectal cancer (CRC) through various biological processes. LncRNA expression can regulate autophagy, which plays dual roles in the initiation and progression of cancers, including CRC. Abnormal expression of lncRNAs is associated with the emergence of chemoresistance. Moreover, it has been confirmed that targeting autophagy through lncRNA regulation could be a viable approach for combating chemoresistance. Two recent studies titled "Human β-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long non-coding RNA TCONS_00014506" and "Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription" revealed novel insights into lncRNAs associated with autophagy and oxaliplatin resistance in CRC, respectively. In this editorial, we particularly focus on the regulatory role of lncRNAs in CRC-related autophagy and chemoresistance since the regulation of chemotherapeutic sensitivity by intervening with the lncRNAs involved in the autophagy process has become a promising new approach for cancer treatment.
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Affiliation(s)
- Jia-Mei Yu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Chong-Qi Sun
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Huan-Huan Xu
- Department of Hematology and Oncology, Department of Geriatric Lung Cancer Research Laboratory, Jiangsu Province Geriatric Hospital, Nanjing 210009, Jiangsu Province, China
| | - Ya-Li Jiang
- Central Laboratory, The Friendship Hospital of Ili Kazakh Autonomous Prefecture, Ili & Jiangsu Joint Institute of Health, Yining 835000, Xinjiang Uyghur Autonomous Region, China
| | - Xing-Yu Jiang
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Si-Qi Ni
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Ting-Yu Zhao
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
| | - Ling-Xiang Liu
- Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
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10
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Tai F, Zhai R, Ding K, Zhang Y, Yang H, Li H, Wang Q, Cao Z, Ge C, Fu H, Xiao F, Zheng X. Long non‑coding RNA lung cancer‑associated transcript 1 regulates ferroptosis via microRNA‑34a‑5p‑mediated GTP cyclohydrolase 1 downregulation in lung cancer cells. Int J Oncol 2024; 64:64. [PMID: 38757341 PMCID: PMC11095600 DOI: 10.3892/ijo.2024.5652] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Accepted: 04/09/2024] [Indexed: 05/18/2024] Open
Abstract
Ferroptosis, a recently discovered type of programmed cell death triggered by excessive accumulation of iron‑dependent lipid peroxidation, is linked to several malignancies, including non‑small cell lung cancer. Long non‑coding RNAs (lncRNAs) are involved in ferroptosis; however, data on their role and mechanism in cancer therapy remains limited. Therefore, the aim of the present study was to identify ferroptosis‑associated mRNAs and lncRNAs in A549 lung cancer cells treated with RAS‑selective lethal 3 (RSL3) and ferrostatin‑1 (Fer‑1) using RNA sequencing. The results demonstrated that lncRNA lung cancer‑associated transcript 1 (LUCAT1) was significantly upregulated in lung adenocarcinoma and lung squamous cell carcinoma tissues. Co‑expression analysis of differentially expressed mRNAs and lncRNAs suggested that LUCAT1 has a crucial role in ferroptosis. LUCAT1 expression was markedly elevated in A549 cells treated with RSL3, which was prevented by co‑incubation with Fer‑1. Functionally, overexpression of LUCAT1 facilitated cell proliferation and reduced the occurrence of ferroptosis induced by RSL3 and Erastin, while inhibition of LUCAT1 expression reduced cell proliferation and increased ferroptosis. Mechanistically, downregulation of LUCAT1 resulted in the downregulation of both GTP cyclohydrolase 1 (GCH1) and ferroptosis suppressor protein 1 (FSP1). Furthermore, inhibition of LUCAT1 expression upregulated microRNA (miR)‑34a‑5p and then downregulated GCH1. These results indicated that inhibition of LUCAT1 expression promoted ferroptosis by modulating the downregulation of GCH1, mediated by miR‑34a‑5p. Therefore, the combination of knocking down LUCAT1 expression with ferroptosis inducers may be a promising strategy for lung cancer treatment.
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Affiliation(s)
- Fumin Tai
- Department of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China
| | - Rui Zhai
- Department of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China
| | - Kexin Ding
- Department of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China
| | - Yaocang Zhang
- Department of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China
| | - Hexi Yang
- Department of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China
| | - Hujie Li
- Department of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China
| | - Qiong Wang
- Department of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China
| | - Zhengyue Cao
- Department of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China
| | - Changhui Ge
- Department of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China
| | - Hanjiang Fu
- Department of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China
| | - Fengjun Xiao
- Department of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China
| | - Xiaofei Zheng
- Department of Experimental Hematology and Biochemistry, Beijing Key Laboratory for Radiobiology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China
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11
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Peng H, Huang Y, Wei G, Pang Y, Yuan H, Zou X, Xie Y, Chen W. Testicular Toxicity in Rats Exposed to AlCl 3: a Proteomics Study. Biol Trace Elem Res 2024; 202:1084-1102. [PMID: 37382810 DOI: 10.1007/s12011-023-03745-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 06/22/2023] [Indexed: 06/30/2023]
Abstract
Aluminum contamination is a growing environmental and public health concern, and aluminum testicular toxicity has been reported in male rats; however, the underlying mechanisms of this toxicity are unclear. The objective of this study was to investigate the effects of exposure to aluminum chloride (AlCl3) on alterations in the levels of sex hormones (testosterone [T], luteinizing hormone [LH], and follicle-stimulating hormone [FSH]) and testicular damage. Additionally, the mechanisms of toxicity in the testes of AlCl3-exposed rats were analyzed by proteomics. Three different concentrations of AlCl3 were administered to rats. The results demonstrated a decrease in T, LH, and FSH levels with increasing concentrations of AlCl3 exposure. HE staining results revealed that the spermatogenic cells in the AlCl3-exposed rats were widened, disorganized, or absent, with increased severe tissue destruction at higher concentrations of AlCl3 exposure. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses revealed that differentially expressed proteins (DEPs) after AlCl3 exposure were primarily associated with various metabolic processes, sperm fibrous sheath, calcium-dependent protein binding, oxidative phosphorylation, and ribosomes. Subsequently, DEPs from each group were subjected to protein-protein interaction (PPI) analysis followed by the screening of interactional key DEPs. Western blot experiments validated the proteomics data, revealing the downregulation of sperm-related DEPs (AKAP4, ODF1, and OAZ3) and upregulation of regulatory ribosome-associated protein (UBA52) and mitochondrial ribosomal protein (MRPL32). These findings provide a basis for studying the mechanism of testicular toxicity due to AlCl3 exposure.
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Affiliation(s)
- Huixin Peng
- The Affiliated Hospital of You jiang Medical University for Nationalities, Baise, 533000, Guangxi, China
- Graduate School of You jiang Medical University for Nationalities, Baise, 533000, Guangxi, China
| | - Yanxin Huang
- The Affiliated Hospital of You jiang Medical University for Nationalities, Baise, 533000, Guangxi, China
- Graduate School of You jiang Medical University for Nationalities, Baise, 533000, Guangxi, China
| | - Guangji Wei
- The Affiliated Hospital of You jiang Medical University for Nationalities, Baise, 533000, Guangxi, China
- Graduate School of You jiang Medical University for Nationalities, Baise, 533000, Guangxi, China
| | - Yanfang Pang
- The Affiliated Hospital of You jiang Medical University for Nationalities, Baise, 533000, Guangxi, China
- Graduate School of You jiang Medical University for Nationalities, Baise, 533000, Guangxi, China
| | - Huixiong Yuan
- The Affiliated Hospital of You jiang Medical University for Nationalities, Baise, 533000, Guangxi, China
- Graduate School of You jiang Medical University for Nationalities, Baise, 533000, Guangxi, China
| | - Xiong Zou
- Guangxi Key Laboratory of reproductive health and birth defect prevention, Nanning, 530000, Guangxi, China
| | - Yu'an Xie
- Guangxi Key Laboratory of reproductive health and birth defect prevention, Nanning, 530000, Guangxi, China.
| | - Wencheng Chen
- The Affiliated Hospital of You jiang Medical University for Nationalities, Baise, 533000, Guangxi, China.
- Graduate School of You jiang Medical University for Nationalities, Baise, 533000, Guangxi, China.
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12
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Tong L, Zheng X, Wang T, Gu W, Shen T, Yuan W, Wang S, Xing S, Liu X, Zhang C, Zhang C. Inhibition of UBA52 induces autophagy via EMC6 to suppress hepatocellular carcinoma tumorigenesis and progression. J Cell Mol Med 2024; 28:e18164. [PMID: 38445807 PMCID: PMC10915828 DOI: 10.1111/jcmm.18164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 01/08/2024] [Accepted: 01/24/2024] [Indexed: 03/07/2024] Open
Abstract
Ubiquitin A-52 residue ribosomal protein fusion product 1 (UBA52) has a role in the occurrence and development of tumours. However, the mechanism by which UBA52 regulates hepatocellular carcinoma (HCC) tumorigenesis and progression remains poorly understood. By using the Cell Counting Kit (CCK-8), colony formation, wound healing and Transwell assays, we assessed the effects of UBA52 knockdown and overexpression on the proliferation and migration of HCC cells in vitro. By establishing subcutaneous and metastatic tumour models in nude mice, we evaluated the effects of UBA52 on HCC cell proliferation and migration in vivo. Through bioinformatic analysis of data from the Gene Expression Profiling Interactive Analysis (GEPIA) and The Cancer Genome Atlas (TCGA) databases, we discovered that UBA52 is associated with autophagy. In addition, we discovered that HCC tissues with high UBA52 expression had a poor prognosis in patients. Moreover, knockdown of UBA52 reduced HCC cell growth and metastasis both in vitro and in vivo. Mechanistically, knockdown of UBA52 induced autophagy through EMC6 in HCC cells. These findings suggest that UBA52 promoted the proliferation and migration of HCC cells through autophagy regulation via EMC6 and imply that UBA52 may be a viable novel treatment target for HCC patients.
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Affiliation(s)
- Li Tong
- Department of General SurgeryThe First Affiliated Hospital of Anhui Medical UniversityHefeiChina
| | - Xiaofei Zheng
- Department of General SurgeryThe First Affiliated Hospital of Anhui Medical UniversityHefeiChina
| | - Tianqi Wang
- Department of General SurgeryThe First Affiliated Hospital of Anhui Medical UniversityHefeiChina
| | - Wang Gu
- Department of General SurgeryThe First Affiliated Hospital of Anhui Medical UniversityHefeiChina
| | - Tingting Shen
- Department of PathologyThe First Affiliated Hospital of Anhui Medical UniversityHefeiChina
| | - Wenkang Yuan
- Department of General SurgeryThe First Affiliated Hospital of Anhui Medical UniversityHefeiChina
| | - Siyu Wang
- Department of General SurgeryThe First Affiliated Hospital of Anhui Medical UniversityHefeiChina
| | - Songlin Xing
- Department of General SurgeryThe First Affiliated Hospital of Anhui Medical UniversityHefeiChina
| | - Xiaoying Liu
- College of Life Sciences of Anhui Medical UniversityHefeiChina
| | - Chong Zhang
- Department of General SurgeryThe First Affiliated Hospital of Anhui Medical UniversityHefeiChina
| | - Chao Zhang
- Department of General SurgeryThe First Affiliated Hospital of Anhui Medical UniversityHefeiChina
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13
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Ding H, Shi H, Chen W, Liu Z, Yang Z, Li X, Qiu Z, Zhuo H. Identification of Key Prognostic Alternative Splicing Events of Costimulatory Molecule-Related Genes in Colon Cancer. Comb Chem High Throughput Screen 2024; 27:1900-1912. [PMID: 37957898 DOI: 10.2174/0113862073249972231026060301] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 09/08/2023] [Accepted: 10/02/2023] [Indexed: 11/15/2023]
Abstract
OBJECTIVE This study aimed to explore the key alternative splicing events in costimulatory molecule-related genes in colon cancer and to determine their correlation with prognosis. METHODS Gene expression RNA-sequencing data, clinical data, and SpliceSeq data of colon cancer were obtained from The Cancer Genome Atlas. Differentially expressed alternative splicing events in genes were identified, Followed by correlation analysis of genes corresponding to differentially expressed alternative splicing events with costimulatory molecule-related genes. Survival analysis was conducted using differentially expressed alternative splicing events in these genes and a prognostic model was constructed. Functional enrichment, proteinprotein interaction network, and splicing factor analyses were performed. RESULTS In total, 6504 differentially expressed alternative splicing events in 3949 genes were identified between tumor and normal tissues. Correlation analysis revealed 3499 differentially expressed alternative splicing events in 2168 costimulatory molecule-related genes. Moreover, 328 differentially expressed alternative splicing events in 288 costimulatory molecule-related genes were associated with overall survival. The prognostic models constructed using these showed considerable power in predicting survival. The ubiquitin A-52 residue ribosomal protein fusion product 1 and ribosomal protein S9 were the hub nodes in the protein-protein interaction network. Furthermore, one splicing factor, splicing factor proline and glutamine-rich, was significantly associated with patient prognosis. Four splicing factor-alternative splicing pairs were obtained from four alternative splicing events in three genes: TBC1 domain family member 8 B, complement factor H, and mitochondrial fission 1. CONCLUSION The identified differentially expressed alternative splicing events of costimulatory molecule-related genes may be used to predict patient prognosis and immunotherapy responses in colon cancer.
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Affiliation(s)
- Hao Ding
- Department of General Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai, China
| | - Huiwen Shi
- Department of General Surgery, No. 971 Hospital of PLA Navy, Shandong, China
| | - Weifeng Chen
- Department of Oncology, Huangdao District Hospital of Traditional Chinese Medicine, Shandong, China
| | - Zhisheng Liu
- Department of General Surgery, Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Shandong, China
| | - Zhi Yang
- The IVD Medical Marketing Department, 3D Medicines Inc., Shadong, China
| | - Xiaochuan Li
- Department of General Surgery, Qingdao Municipal Hospital, Shandong, China
| | - Zhichao Qiu
- Department of Oncology, Shunde Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Hongqing Zhuo
- Department of Gastrointestinal Surgery, Provincial Hospital Affiliated to Shandong First Medical University, Shadong, China
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14
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Lin H, Hu S, Li Y, Li S, Teng D, Yang Y, Liu B, Du X. H3K27ac-activated LncRNA NUTM2A-AS1 Facilitated the Progression of Colorectal Cancer Cells via MicroRNA-126-5p/FAM3C Axis. Curr Cancer Drug Targets 2024; 24:1222-1234. [PMID: 38347779 DOI: 10.2174/0115680096277956240119065938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Revised: 01/04/2024] [Accepted: 01/10/2024] [Indexed: 09/25/2024]
Abstract
OBJECTIVE Long non-coding RNAs (lncRNAs) are of great importance in the process of colorectal cancer (CRC) tumorigenesis and progression. However, the functions and underlying molecular mechanisms of the majority of lncRNAs in CRC still lack clarity. METHODS A Quantitative real-time polymerase chain reaction (qRT-PCR) was employed to detect lncRNA NUTM2A-AS1 expression in CRC cell lines. Cell counting kit 8 (CCK-8) assay and flow cytometry were used to examine the biological functions of lncRNA NUTM2A-AS1 in the proliferation and apoptosis of CRC cells. RT-qPCR and western blot were implemented for the detection of cell proliferation-, apoptosis-related proteins, and FAM3C. Bioinformatics analysis and dual- luciferase reporter assays were utilized to identify the mutual regulatory mechanism of ceRNAs. RESULTS lncRNA NUTM2A-AS1 notably elevated in CRC cell lines and the silenced of NUTM2A- AS1 declined proliferation and facilitated apoptosis. Mechanistically, NUTM2A-AS1 was transcriptionally activated by histone H3 on lysine 27 acetylation (H3K27ac) enriched at its promoter region, and NUTM2A-AS1 acted as a sponge for miR-126-5p, leading to the upregulation of FAM3C expression in CRC cell lines. CONCLUSION Our research proposed NUTM2A-AS1 as an oncogenic lncRNA that facilitates CRC malignancy by upregulating FAM3C expression, which might provide new insight and a promising therapeutic target for the diagnosis and treatment of CRC.
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Affiliation(s)
- Haiguan Lin
- Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
- Department of General Surgery, PLA Strategic Support Force Characteristic Medical Center, Beijing, China
| | - Shidong Hu
- Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Yuxuan Li
- Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Songyan Li
- Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Da Teng
- Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Yan Yang
- Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Boyan Liu
- Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
| | - Xiaohui Du
- Department of General Surgery, the First Medical Centre, Chinese PLA General Hospital, Beijing, China
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15
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Cui H, Lian J, Xu B, Yu Z, Xiang H, Shi J, Gao Y, Han T. Identification of a bile acid and bile salt metabolism-related lncRNA signature for predicting prognosis and treatment response in hepatocellular carcinoma. Sci Rep 2023; 13:19512. [PMID: 37945918 PMCID: PMC10636107 DOI: 10.1038/s41598-023-46805-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 11/05/2023] [Indexed: 11/12/2023] Open
Abstract
Bile acids and salts have been shown to play a role in liver carcinogenesis through DNA damage, inflammation, and tumor proliferation. However, the correlation between bile acid metabolism and hepatocellular carcinoma (HCC) prognosis remains unclear. This study aimed to identify a predictive signature of bile acid and bile salt metabolism-related long non-coding RNAs (lncRNAs) for HCC prognosis and treatment response. The study used HCC RNA-sequencing data and corresponding clinical and prognostic data from The Cancer Genome Atlas. A prognostic model consisting of five bile acid and bile salt metabolism-related lncRNAs was developed and evaluated in a training set, a validation set and an external set. The model demonstrated good performance in predicting HCC prognosis and was shown to be an independent biomarker for prognosis. Additionally, our study revealed a significant association between the signature and immune cell infiltration, as well as its predictive value for therapeutic responses to both immunotherapy and chemotherapy. Furthermore, three LncRNAs (LUCAT1, AL031985.3 and AC015908.3) expression levels in our signature were validated through qRT-PCR in a cohort of 50 pairs of HCC patient tumor samples and corresponding adjacent non-tumor samples, along with 10 samples of normal liver tissue adjacent to benign lesions. These findings suggest that this novel bile acid and bile salt metabolism-related lncRNA signature can independently predict the prognosis of patients with HCC and may be utilized as a potential predictor of response to treatment in this setting.
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Affiliation(s)
- Hao Cui
- Department of Gastroenterology and Hepatology, The Third Central Clinical College of Tianjin Medical University, Tianjin, China
- Department of Gastroenterology and Hepatology, Tianjin Union Medical Center, Tianjin Medical University, Tianjin, China
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin, China
| | - Jia Lian
- Department of Gastroenterology and Hepatology, The Third Central Clinical College of Tianjin Medical University, Tianjin, China
- Department of Gastroenterology and Hepatology, Tianjin Union Medical Center, Tianjin Medical University, Tianjin, China
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin, China
| | - Baiguo Xu
- Department of Gastroenterology and Hepatology, The Third Central Clinical College of Tianjin Medical University, Tianjin, China
- Department of Gastroenterology and Hepatology, Tianjin Union Medical Center, Tianjin Medical University, Tianjin, China
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin, China
| | - Zhenjun Yu
- Department of Gastroenterology and Hepatology, The Third Central Clinical College of Tianjin Medical University, Tianjin, China
| | - Huiling Xiang
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin, China.
| | - Jingxiang Shi
- Department of Hepatobiliary Surgery, The Third Central Hospital of Tianjin, Tianjin, China.
| | - Yingtang Gao
- Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin Institute of Hepatobiliary Disease, Nankai University Affinity the Third Central Hospital, Tianjin, China.
| | - Tao Han
- Department of Gastroenterology and Hepatology, Tianjin Union Medical Center, Tianjin Medical University, Tianjin, China.
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Zhang ZD, Hou XR, Cao XL, Wang XP. Long non‑coding RNAs, lipid metabolism and cancer (Review). Exp Ther Med 2023; 26:470. [PMID: 37664674 PMCID: PMC10468807 DOI: 10.3892/etm.2023.12169] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 07/14/2023] [Indexed: 09/05/2023] Open
Abstract
Cancer has emerged as the most common cause of death in China. The change in lipid metabolism has been confirmed to have a role in several tumor types, such as esophageal, gastric, colorectal and liver cancer. Cancer cells use lipid metabolism for energy and then rapidly proliferate, invade and migrate. The main pathway by which cancer cell lipid metabolism influences cancer progression is increased fatty acid synthesis. Long non-coding (lnc)RNAs are important ncRNAs that were indicated to have significant roles in the development of human tumors. They are considered potential tumor biomarkers. Increased lipid synthesis or uptake due to deregulation of lncRNAs contributes to rapid tumor growth. In the present review, current studies on the relationship between lncRNAs, lipid metabolism and the occurrence and development of tumors were collated and summarized, and their mechanism of action was discussed. The review is expected to provide a theoretical basis for tumor treatment and prognosis evaluation based on the effective regulation of lncRNAs and lipid metabolism.
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Affiliation(s)
- Zhen-Dong Zhang
- Graduate School, Xizang Minzu University, Xianyang, Shaanxi 712082, P.R. China
- Key Laboratory of High-Altitude Hypoxia Environment and Life Health, Joint Laboratory for Research on Active Components and Pharmacological Mechanism of Tibetan Medicine, Materia Medica of Tibetan Medical Research Center of Tibet, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, P.R. China
| | - Xin-Rui Hou
- Graduate School, Xizang Minzu University, Xianyang, Shaanxi 712082, P.R. China
- Key Laboratory of High-Altitude Hypoxia Environment and Life Health, Joint Laboratory for Research on Active Components and Pharmacological Mechanism of Tibetan Medicine, Materia Medica of Tibetan Medical Research Center of Tibet, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, P.R. China
| | - Xiao-Lan Cao
- Graduate School, Xizang Minzu University, Xianyang, Shaanxi 712082, P.R. China
- Key Laboratory of High-Altitude Hypoxia Environment and Life Health, Joint Laboratory for Research on Active Components and Pharmacological Mechanism of Tibetan Medicine, Materia Medica of Tibetan Medical Research Center of Tibet, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, P.R. China
| | - Xiao-Ping Wang
- Key Laboratory of High-Altitude Hypoxia Environment and Life Health, Joint Laboratory for Research on Active Components and Pharmacological Mechanism of Tibetan Medicine, Materia Medica of Tibetan Medical Research Center of Tibet, School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, P.R. China
- School of Medicine, Xizang Minzu University, Xianyang, Shaanxi 712082, P.R. China
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Yao S, Wang S, Zheng M, Wang Z, Liu Z, Wang ZL, Li L. Implantable, Biodegradable, and Wireless Triboelectric Devices for Cancer Therapy through Disrupting Microtubule and Actins Dynamics. ADVANCED MATERIALS (DEERFIELD BEACH, FLA.) 2023; 35:e2303962. [PMID: 37392034 DOI: 10.1002/adma.202303962] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 06/27/2023] [Accepted: 06/28/2023] [Indexed: 07/02/2023]
Abstract
Electric-field-based stimulation is emerging as a new cancer therapeutic modality through interfering with cell mitosis. To address its limitations of complicated wire connections, bulky devices, and coarse spatial resolution, an improved and alternative method is proposed for wirelessly delivering electrical stimulation into tumor tissues through designing an implantable, biodegradable, and wirelessly controlled therapeutic triboelectric nanogenerator (ET-TENG). With the excitation of ultrasound (US) to the ET-TENG, the implanted ET-TENG can generate an alternating current voltage and concurrently release the loaded anti-mitotic drugs into tumor tissues, which synergistically disrupts the assembly of microtubules and filament actins, induces cell cycle arrest, and finally enhances cell death. With the assistance of US, the device can be completely degraded after the therapy, getting free of a secondary surgical extraction. The device can not only work around those unresectable tumors, but also provides a new application of wireless electric field in cancer therapy.
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Affiliation(s)
- Shuncheng Yao
- Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 101400, P. R. China
- School of Nanoscience and Technology, University of Chinese Academy of Sciences, Beijing, 101400, P. R. China
| | - Shaobo Wang
- Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 101400, P. R. China
- Center on Nanoenergy Research, Guangxi University, Nanning, 530004, P. R. China
| | - Minjia Zheng
- Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 101400, P. R. China
- Center on Nanoenergy Research, Guangxi University, Nanning, 530004, P. R. China
| | - Zhuo Wang
- Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 101400, P. R. China
| | - Zhirong Liu
- Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 101400, P. R. China
- School of Nanoscience and Technology, University of Chinese Academy of Sciences, Beijing, 101400, P. R. China
| | - Zhong Lin Wang
- Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 101400, P. R. China
- School of Nanoscience and Technology, University of Chinese Academy of Sciences, Beijing, 101400, P. R. China
- Center on Nanoenergy Research, Guangxi University, Nanning, 530004, P. R. China
- School of Materials Science and Engineering, Georgia Institute of Technology, Atlanta, GA, 30332-0245, USA
| | - Linlin Li
- Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 101400, P. R. China
- School of Nanoscience and Technology, University of Chinese Academy of Sciences, Beijing, 101400, P. R. China
- Center on Nanoenergy Research, Guangxi University, Nanning, 530004, P. R. China
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18
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Zhang Z, Wang X. Roles of long non-coding RNAs in digestive tract cancer and their clinical application. Zhejiang Da Xue Xue Bao Yi Xue Ban 2023; 52:451-459. [PMID: 37643979 PMCID: PMC10495243 DOI: 10.3724/zdxbyxb-2023-0169] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 08/02/2023] [Indexed: 08/24/2023]
Abstract
Long non-coding RNAs (lncRNAs) are strongly related to the occurrence and development of digestive tract cancer in human. Firstly, lncRNAs target and regulate the expression of downstream cancer genes to affect the growth, metastasis, apoptosis, metabolism and immune escape of cancer cells. Secondly, lncRNAs are considered to be important regulating factors for lipid metabolism in cancer, which is related to signaling pathways of adipogenesis and involved in the occurrence and development of digestive tract cancer. Finally, lncRNAs have application value in the diagnosis and treatment of digestive tract cancer. For example, lncRNAMALAT1 has been reported as a target for diagnosis and treatment of hepatocellular carcinoma. This article reviews current progress on the regulatory role of lncRNAs in digestive tract cancer, to provide references for the research and clinical application in the prevention and treatment of digestive tract cancer.
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Affiliation(s)
- Zhendong Zhang
- School of Medicine, Xizang Minzu University, Key Laboratory of High Altitude Hypoxia Environment and Life Health, Joint Laboratory for Research on Active Components and Pharmacological Mechanism of Tibetan Materia Medica of Tibetan Medical Research Center of Tibet, Xianyang 712082, Shaanxi Province, China.
| | - Xiaoping Wang
- School of Medicine, Xizang Minzu University, Key Laboratory of High Altitude Hypoxia Environment and Life Health, Joint Laboratory for Research on Active Components and Pharmacological Mechanism of Tibetan Materia Medica of Tibetan Medical Research Center of Tibet, Xianyang 712082, Shaanxi Province, China.
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19
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Shomali N, Kamrani A, Nasiri H, Heris JA, Shahabi P, Yousefi M, Mohammadinasab R, Sadeghvand S, Akbari M. An updated review of a novel method for examining P53 mutations in different forms of cancer. Pathol Res Pract 2023; 248:154585. [PMID: 37302277 DOI: 10.1016/j.prp.2023.154585] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/02/2023] [Revised: 05/27/2023] [Accepted: 05/28/2023] [Indexed: 06/13/2023]
Abstract
In the past fifteen years, it has been clear that tumor-associated p53 mutations can cause behaviors distinct from those brought on by a simple loss of p53's tumor-suppressive function in its wild-type form. Many of these mutant p53 proteins develop oncogenic characteristics that allow them to encourage cell survival, invasion, and metastasis. But it is now understood that the immune response is also significantly influenced by the cancer cell's p53 status. The recruitment and activity of myeloid and T cells can be impacted by p53 loss or mutation in malignancies, allowing immune evasion and accelerating cancer growth. Additionally, p53 can work in immune cells, which can have various effects that either hinder or assist the growth of tumors. In this review article, we examined different mutations of P53 in some significant cancers, such as liver, colorectal, and prostate, and reviewed some new therapeutic approaches.
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Affiliation(s)
- Navid Shomali
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran
| | - Amin Kamrani
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Hadi Nasiri
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Javad Ahmadian Heris
- Department of Allergy and Clinical Immunology, Pediatric Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Parviz Shahabi
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Physiology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mehdi Yousefi
- Department of Immunology, Faculty of Medicine, Tabriz University of Medical Science, Tabriz, Iran; Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Reza Mohammadinasab
- Department of History of Medicine, School of Traditional Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Shahram Sadeghvand
- Pediatrics Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Morteza Akbari
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
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20
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Liang XR, Liu YF, Chen F, Zhou ZX, Zhang LJ, Lin ZJ. Cell Cycle-Related lncRNAs as Innovative Targets to Advance Cancer Management. Cancer Manag Res 2023; 15:547-561. [PMID: 37426392 PMCID: PMC10327678 DOI: 10.2147/cmar.s407371] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2023] [Accepted: 06/13/2023] [Indexed: 07/11/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) are non-coding RNAs (ncRNAs) longer than 200nt. They have complex biological functions and take part in multiple fundamental biological processes, such as cell proliferation, differentiation, survival and apoptosis. Recent studies suggest that lncRNAs modulate critical regulatory proteins involved in cancer cell cycle, such as cyclin, cell cycle protein-dependent kinases (CDK) and cell cycle protein-dependent kinase inhibitors (CKI) through different mechanisms. To clarify the role of lncRNAs in the regulation of cell cycle will provide new ideas for design of antitumor therapies which intervene with the cell cycle progression. In this paper, we review the recent studies about the controlling of lncRNAs on cell cycle related proteins such as cyclin, CDK and CKI in different cancers. We further outline the different mechanisms involved in this regulation and describe the emerging role of cell cycle-related lncRNAs in cancer diagnosis and therapy.
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Affiliation(s)
- Xiao-Ru Liang
- Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Weifang Medical University, Weifang, People’s Republic of China
| | - Yan-Fei Liu
- Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Weifang Medical University, Weifang, People’s Republic of China
| | - Feng Chen
- Department of General Surgery, Weifang Traditional Chinese Hospital, Weifang, Shandong, People’s Republic of China
| | - Zhi-Xia Zhou
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, People’s Republic of China
| | - Li-Jie Zhang
- Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Weifang Medical University, Weifang, People’s Republic of China
| | - Zhi-Juan Lin
- Key Laboratory of Immune Microenvironment and Inflammatory Disease Research in Universities of Shandong Province, School of Basic Medical Sciences, Weifang Medical University, Weifang, People’s Republic of China
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21
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Eastham MJ, Pelava A, Wells GR, Watkins NJ, Schneider C. RPS27a and RPL40, Which Are Produced as Ubiquitin Fusion Proteins, Are Not Essential for p53 Signalling. Biomolecules 2023; 13:898. [PMID: 37371478 DOI: 10.3390/biom13060898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Revised: 05/24/2023] [Accepted: 05/26/2023] [Indexed: 06/29/2023] Open
Abstract
Two of the four human ubiquitin-encoding genes express ubiquitin as an N-terminal fusion precursor polypeptide, with either ribosomal protein (RP) RPS27a or RPL40 at the C-terminus. RPS27a and RPL40 have been proposed to be important for the induction of the tumour suppressor p53 in response to defects in ribosome biogenesis, suggesting that they may play a role in the coordination of ribosome production, ubiquitin levels and p53 signalling. Here, we report that RPS27a is cleaved from the ubiquitin-RP precursor in a process that appears independent of ribosome biogenesis. In contrast to other RPs, the knockdown of either RPS27a or RPL40 did not stabilise the tumour suppressor p53 in U2OS cells. Knockdown of neither protein blocked p53 stabilisation following inhibition of ribosome biogenesis by actinomycin D, indicating that they are not needed for p53 signalling in these cells. However, the knockdown of both RPS27a and RPL40 in MCF7 and LNCaP cells robustly induced p53, consistent with observations made with the majority of other RPs. Importantly, RPS27a and RPL40 are needed for rRNA production in all cell lines tested. Our data suggest that the role of RPS27a and RPL40 in p53 signalling, but not their importance in ribosome biogenesis, differs between cell types.
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Affiliation(s)
- Matthew John Eastham
- Biosciences Institute, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
| | - Andria Pelava
- Biosciences Institute, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
| | - Graeme Raymond Wells
- Biosciences Institute, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
| | - Nicholas James Watkins
- Biosciences Institute, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
| | - Claudia Schneider
- Biosciences Institute, The Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
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22
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Yu R, Wang Y, Liang Q, Xu Y, Yusf AE, Sun L. Identification of potential biomarkers and pathways for sepsis using RNA sequencing technology and bioinformatic analysis. Heliyon 2023; 9:e15034. [PMID: 37089399 PMCID: PMC10113783 DOI: 10.1016/j.heliyon.2023.e15034] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 03/22/2023] [Accepted: 03/24/2023] [Indexed: 04/05/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) has been proven by many to play a crucial part in the process of sepsis. To obtain a better understanding of sepsis, the molecular biomarkers associated with it, and its possible pathogenesis, we obtained data from RNA-sequencing analysis using serum from three sepsis patients and three healthy controls (HCs). Using edgeR (one of the Bioconductor software package), we identified 1118 differentially expressed mRNAs (DEmRNAs) and 1394 differentially expressed long noncoding RNAs (DElncRNAs) between sepsis patients and HCs. We identified the biological functions of these disordered genes using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analyses. The GO analysis showed that the homophilic cell adhesion via plasma membrane adhesion molecules was the most significantly enriched category. The KEGG signaling pathway analysis indicated that the differentially expressed genes (DEGs) were most significantly enriched in retrograde endocannabinoid signaling. Using STRING, a protein-protein interaction network was also created, and Cytohubba was used to determine the top 10 hub genes. To examine the relationship between the hub genes and sepsis, we examined three datasets relevant to sepsis that were found in the gene expression omnibus (GEO) database. PTEN and HIST2H2BE were recognized as hub gene in both GSE4607, GSE26378, and GSE9692 datasets. The receiver operating characteristic (ROC) curves indicate that PTEN and HIST2H2BE have good diagnostic value for sepsis. In conclusion, this two hub genes may be biomarkers for the early diagnosis of sepsis, our findings should deepen our understanding of the pathogenesis of sepsis.
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23
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Chen LJ, Chen X, Niu XH, Peng XF. LncRNAs in colorectal cancer: Biomarkers to therapeutic targets. Clin Chim Acta 2023; 543:117305. [PMID: 36966964 DOI: 10.1016/j.cca.2023.117305] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 03/18/2023] [Accepted: 03/20/2023] [Indexed: 03/29/2023]
Abstract
Colorectal cancer (CRC) is the third leading cause of cancer-related death in men and women worldwide. As early detection is associated with lower mortality, novel biomarkers are urgently needed for timely diagnosis and appropriate management of patients to achieve the best therapeutic response. Long noncoding RNAs (lncRNAs) have been reported to play essential roles in CRC progression. Accordingly, the regulatory roles of lncRNAs should be better understood in general and for identifying diagnostic, prognostic and predictive biomarkers in CRC specifically. In this review, the latest advances on the potential diagnostic and prognostic lncRNAs as biomarkers in CRC samples were highlighted, Current knowledge on dysregulated lncRNAs and their potential molecular mechanisms were summarized. The potential therapeutic implications and challenges for future and ongoing research in the field were also discussed. Finally, novel insights on the underlying mechanisms of lncRNAs were examined as to their potential role as biomarkers and therapeutic targets in CRC. This review may be used to design future studies and advanced investigations on lncRNAs as biomarkers for the diagnosis, prognosis and therapy in CRC.
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Affiliation(s)
- Ling-Juan Chen
- Department of Clinical Laboratory, Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, Guangdong Province, China
| | - Xiang Chen
- Department of General Surgery, Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, Guangdong Province, China
| | - Xiao-Hua Niu
- Department of General Surgery, Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, Guangdong Province, China
| | - Xiao-Fei Peng
- Department of General Surgery, Qingyuan People's Hospital, The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan 511518, Guangdong Province, China.
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24
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Luo ZD, Wang YF, Zhao YX, Yu LC, Li T, Fan YJ, Zeng SJ, Zhang YL, Zhang Y, Zhang X. Emerging roles of non-coding RNAs in colorectal cancer oxaliplatin resistance and liquid biopsy potential. World J Gastroenterol 2023; 29:1-18. [PMID: 36683709 PMCID: PMC9850945 DOI: 10.3748/wjg.v29.i1.1] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 10/11/2022] [Accepted: 11/04/2022] [Indexed: 01/04/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common malignancies of the digestive tract, with the annual incidence and mortality increasing consistently. Oxaliplatin-based chemotherapy is a preferred therapeutic regimen for patients with advanced CRC. However, most patients will inevitably develop resistance to oxaliplatin. Many studies have reported that non-coding RNAs (ncRNAs), such as microRNAs, long non-coding RNAs, and circular RNAs, are extensively involved in cancer progression. Moreover, emerging evidence has revealed that ncRNAs mediate chemoresistance to oxaliplatin by transcriptional and post-transcriptional regulation, and by epigenetic modification. In this review, we summarize the mechanisms by which ncRNAs regulate the initiation and development of CRC chemoresistance to oxaliplatin. Furthermore, we investigate the clinical application of ncRNAs as promising biomarkers for liquid CRC biopsy. This review provides new insights into overcoming oxaliplatin resistance in CRC by targeting ncRNAs.
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Affiliation(s)
- Zheng-Dong Luo
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Yi-Feng Wang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Yu-Xiao Zhao
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Long-Chen Yu
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Tian Li
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Ying-Jing Fan
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Shun-Jie Zeng
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Yan-Li Zhang
- Department of Clinical Laboratory, Shandong Provincial Third Hospital, Jinan 250012, Shandong Province, China
| | - Yi Zhang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
| | - Xin Zhang
- Department of Clinical Laboratory, Qilu Hospital of Shandong University, Shandong Engineering Research Center of Biomarker and Artificial Intelligence Application, Jinan 250012, Shandong Province, China
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25
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Long non-coding RNA LUCAT1 regulates the RAS pathway to promote the proliferation and invasion of malignant glioma cells through ABCB1. Exp Cell Res 2022; 421:113390. [PMID: 36270516 DOI: 10.1016/j.yexcr.2022.113390] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 09/22/2022] [Accepted: 10/13/2022] [Indexed: 12/29/2022]
Abstract
Long non-coding RNAs (lncRNAs) are closely related to the occurrence and development of tumors and have gradually become a hot topic in the field of glioma research in recent years. In this study, the role of lung cancer associated transcript 1 (lncRNA LUCAT 1) in glioma occurrence and development, as well as its possible regulatory mechanism, was explored. We utilized the gene chip technology in the preliminary experiment, and based on the experiment results, selected LUCAT1（NONHSAT102745）, which was significantly upregulated in glioma, and ATP-binding cassette Subfamily B member l (ABCB1), which was significantly down-regulated in co-expression analysis, for study. Next, the expression of LUCAT1 and ABCB1 in cells and tissues was immediately evaluated. Subsequently, the cells were transfected with scrambled siRNA, LUCAT1-siRNA/ABCB 1-siRNA, or overexpressed LUCAT1/ABCB1 plasmid + RAS signaling pathway inhibitor-farnesylthiosalicylic acid (FTS). By comparing with the normal combination negative control group, the cell proliferation and invasion ability were evaluated. Finally, subcutaneous tumor formation experiments in the nude mice confirmed the association between LUCAT1 and ABCB1 and RAS signaling pathways. The expression of LUCAT 1 was up-regulated with an increase in WHO grade, and the lncRNA-mRNA co-expression analysis showed that the expression of ABCB1 was low. LUCAT 1 gene knockout reduced the mRNA and protein levels of Ras signaling pathway related factors (Ras, Raf-1, p-AKT, and p-ERK) as regulating ABCB1 expression and inhibiting the ability of tumor in proliferation and invasion no matter in vitro or in vivo. For overexpressing of LUCAT 1, the opposite was true. After we knocked out ABCB1, the LUCAT1 expression was reversely regulated while the level of RAS signaling pathway related factors increased, and the ability of tumors in proliferation and invasion was enhanced. The abnormal LUCAT1 expression affected the biological behaviors of glioma cells, such as proliferation, invasion, etc. by regulating ABCB1 and promoting the activation of the RAS signaling pathway. This provided a new drug target and therapeutic approach for gene therapy of glioma, which is expected to significantly improve the prognosis of relevant patients.
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26
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Yuan X, Ma S, Fa B, Wei T, Ma Y, Wang Y, Lv W, Zhang Y, Zheng J, Chen G, Sun J, Yu Z. A high-efficiency differential expression method for cancer heterogeneity using large-scale single-cell RNA-sequencing data. Front Genet 2022; 13:1063130. [DOI: 10.3389/fgene.2022.1063130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2022] [Accepted: 11/14/2022] [Indexed: 12/03/2022] Open
Abstract
Colorectal cancer is a highly heterogeneous disease. Tumor heterogeneity limits the efficacy of cancer treatment. Single-cell RNA-sequencing technology (scRNA-seq) is a powerful tool for studying cancer heterogeneity at cellular resolution. The sparsity, heterogeneous diversity, and fast-growing scale of scRNA-seq data pose challenges to the flexibility, accuracy, and computing efficiency of the differential expression (DE) methods. We proposed HEART (high-efficiency and robust test), a statistical combination test that can detect DE genes with various sources of differences beyond mean expression changes. To validate the performance of HEART, we compared HEART and the other six popular DE methods on various simulation datasets with different settings by two simulation data generation mechanisms. HEART had high accuracy (F1 score >0.75) and brilliant computational efficiency (less than 2 min) on multiple simulation datasets in various experimental settings. HEART performed well on DE genes detection for the PBMC68K dataset quantified by UMI counts and the human brain single-cell dataset quantified by read counts (F1 score = 0.79, 0.65). By applying HEART to the single-cell dataset of a colorectal cancer patient, we found several potential blood-based biomarkers (CTTN, S100A4, S100A6, UBA52, FAU, and VIM) associated with colorectal cancer metastasis and validated them on additional spatial transcriptomic data of other colorectal cancer patients.
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27
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Zhang F, Zhang G, Zhang H, Pu X, Chi F, Zhang D, Xin X, Gao M, Luo W, Li X. HOXA-AS2 may be a potential prognostic biomarker in human cancers: A meta-analysis and bioinformatics analysis. Front Genet 2022; 13:944278. [PMID: 36437956 PMCID: PMC9686854 DOI: 10.3389/fgene.2022.944278] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Accepted: 10/27/2022] [Indexed: 04/05/2025] Open
Abstract
Background: Dysregulation of long non-coding (lncRNA) has been reported in various solid tumors. HOXA cluster antisense RNA 2 (HOXA-AS2) is a newly identified lncRNA with abnormal expression in several human malignancies. However, its prognostic value remains controversial. This meta-analysis synthesized available data to clarify the association between HOXA-AS2 expression levels and clinical prognosis in multiple cancers. Methods: Four public databases (Embase, PubMed, Web of Science, The Cochrane Library) were used to identify eligible studies. Hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were combined to assess the correlation of HOXA-AS2 expression with survival outcomes and clinicopathological features of cancer patients. Publication bias was measured using Begg's funnel plot and Egger's regression test, and the stability of the combined results was measured using sensitivity analysis. Additionally, multiple public databases were screened and extracted to validate the results of this meta-analysis. Results: The study included 20 studies, containing 1331 patients. The meta-analysis showed that the overexpression of HOXA-AS2 was associated with poor overall survival (HR = 2.06, 95% CI 1.58-2.69, p < 0.001). In addition, the high expression of HOXA-AS2 could forecast advanced tumor stage (OR = 3.89, 95% CI 2.90-5.21, p < 0.001), earlier lymph node metastasis (OR = 3.48, 95% CI 2.29-5.29, p < 0.001), larger tumor size (OR = 2.36, 95% CI 1.52-3.66, p < 0.001) and earlier distant metastasis (OR = 3.54, 95% CI 2.00-6.28, p < 0.001). However, other clinicopathological features, including age (OR = 1.09, 95% CI 0.86-1.38, p = 0.467), gender (OR = 0.92, 95% CI 0.72-1.18, p = 0.496), depth of invasion (OR = 2.13, 95% CI 0.77-5.90, p = 0.146) and differentiation (OR = 1.02, 95% CI 0.65-1.59, p = 0.945) were not significantly different from HOXA-AS2 expression. Conclusion: Our study showed that the overexpression of HOXA-AS2 was related to poor overall survival and clinicopathological features. HOXA-AS2 may serve as a potential prognostic indicator and therapeutic target for tumor treatment.
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Affiliation(s)
- Fan Zhang
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
- Department of Orthopedics, Gansu Provincial Hospital, Lanzhou, China
| | - Guangming Zhang
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
- Department of Orthopedics, Gansu Provincial Hospital, Lanzhou, China
| | - Helin Zhang
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
- Department of Orthopedics, Gansu Provincial Hospital, Lanzhou, China
| | - Xingyu Pu
- Department of Orthopedics, Gansu Provincial Hospital, Lanzhou, China
| | - Fei Chi
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
- Department of Orthopedics, Gansu Provincial Hospital, Lanzhou, China
| | - Dengxiao Zhang
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
- Department of Orthopedics, Gansu Provincial Hospital, Lanzhou, China
| | - Xiaoming Xin
- The First Clinical Medical College of Gansu University of Chinese Medicine (Gansu Provincial Hospital), Lanzhou, China
- Department of Orthopedics, Gansu Provincial Hospital, Lanzhou, China
| | - Mingxuan Gao
- Department of Orthopedics, Gansu Provincial Hospital, Lanzhou, China
| | - Wenyuan Luo
- Department of Orthopedics, Gansu Provincial Hospital, Lanzhou, China
| | - Xingyong Li
- Department of Orthopedics, Gansu Provincial Hospital, Lanzhou, China
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28
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Kalantari S, Kazemi B, Roudi R, Zali H, D'Angelo A, Mohamadkhani A, Madjd Z, Pourshams A. RNA-sequencing for transcriptional profiling of whole blood in early stage and metastatic pancreatic cancer patients. Cell Biol Int 2022; 47:238-249. [PMID: 36229929 DOI: 10.1002/cbin.11924] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Accepted: 09/21/2022] [Indexed: 11/10/2022]
Abstract
We investigated the transcriptional profile of whole blood in early and metastatic stages of pancreatic cancer (PaC) patients to identify potential diagnostic factors for early diagnosis. Blood samples from 18 participants (6 healthy individuals, 6 patients in early stage (I/II) PaC, and 6 patients in metastatic PaC) were analyzed by RNA-sequencing. The expression levels of identified genes were subsequently compared with their expression in pancreatic tumor tissues based on TCGA data reported in UALCAN and GEPIA2 databases. Overall, 331 and 724 genes were identified as differentially expressed genes in early and metastatic stages, respectively. Of these, 146 genes were shared by early and metastatic stages. Upregulation of PTCD3 and UBA52 genes and downregulation of A2M and ARID1B genes in PaC patients were observed from early stage to metastasis. TCGA database showed increasing trend in expression levels of these genes from stage I to IV in pancreatic tumor tissue. Finally, we found that low expression of PTCD3, A2M, and ARID1B genes and high expression of UBA52 gene were positively correlated with PaC patients survival. We identified a four-gene set (PTCD3, UBA52, A2M, and ARID1B) expressed in peripheral blood of early stage and metastatic PaC patients that may be useful for PaC early diagnosis.
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Affiliation(s)
- Sima Kalantari
- Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bahram Kazemi
- Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Raheleh Roudi
- Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA
| | - Hakimeh Zali
- Proteomics Research Center, Shahid Beheshti University of Medical Science, Tehran, Iran.,Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alberto D'Angelo
- Department of Biology and Biochemistry, University of Bath, Bath, UK
| | - Ashraf Mohamadkhani
- Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Zahra Madjd
- Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Akram Pourshams
- Liver and Pancreatobiliary Diseases Research Center, Digestive Disease Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran.,Digestive Oncology Research Center, Digestive Diseases Research Institute, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
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29
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Irfan M, Javed Z, Khan K, Khan N, Docea AO, Calina D, Sharifi-Rad J, Cho WC. Apoptosis evasion via long non-coding RNAs in colorectal cancer. Cancer Cell Int 2022; 22:280. [PMID: 36076273 PMCID: PMC9461221 DOI: 10.1186/s12935-022-02695-8] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 08/31/2022] [Indexed: 01/03/2023] Open
Abstract
Long non-coding RNA (LncRNA) is a novel and diverse class of regulatory transcripts that are frequently dysregulated in numerous tumor types. LncRNAs are involved in a complicated molecular network, regulating gene expression, and modulating diverse cellular activities in different cancers including colorectal cancer (CRC). Evidence indicates that lncRNAs can be used as a potential biomarker for the prognosis and diagnosis of CRC as they are aberrantly expressed in CRC cells. The high expression or silencing of lncRNAs is associated with cell proliferation, invasion, metastasis, chemoresistance and apoptosis in CRC. LncRNAs exert both pro-apoptotic and anti-apoptotic functions in CRC. The expression of some oncogene lncRNAs is upregulated which leads to the inhibition of apoptotic pathways, similarly, the tumor suppressor lncRNAs are downregulated in CRC. In this review, we describe the function and mechanisms of lncRNAs to regulate the expression of genes that are involved directly or indirectly in controlling cellular apoptosis in CRC. Furthermore, we also discussed the different apoptotic pathways in normal cells and the mechanisms by which CRC evade apoptosis.
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Affiliation(s)
- Muhammad Irfan
- Atta-Ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
| | - Zeeshan Javed
- Office for Research Innovation and Commercialization, Lahore Garrison University, Lahore, Pakistan
| | - Khushbukhat Khan
- Atta-Ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
| | - Naila Khan
- Atta-Ur-Rahman School of Applied Biosciences, National University of Sciences and Technology, Islamabad, Pakistan
| | - Anca Oana Docea
- Department of Toxicology, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania
| | - Daniela Calina
- Department of Clinical Pharmacy, University of Medicine and Pharmacy of Craiova, 200349, Craiova, Romania.
| | | | - William C Cho
- Department of Clinical Oncology, Queen Elizabeth Hospital, Kowloon, Hong Kong.
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Yao Q, Zhang X, Chen D. The emerging potentials of lncRNA DRAIC in human cancers. Front Oncol 2022; 12:867670. [PMID: 35992823 PMCID: PMC9386314 DOI: 10.3389/fonc.2022.867670] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 07/11/2022] [Indexed: 12/24/2022] Open
Abstract
Long non-coding RNA (lncRNA) is a subtype of noncoding RNA that has more than 200 nucleotides. Numerous studies have confirmed that lncRNA is relevant during multiple biological processes through the regulation of various genes, thus affecting disease progression. The lncRNA DRAIC, a newly discovered lncRNA, has been found to be abnormally expressed in a variety of diseases, particularly cancer. Indeed, the dysregulation of DRAIC expression is closely related to clinicopathological features. It was also reported that DRAIC is key to biological functions such as cell proliferation, autophagy, migration, and invasion. Furthermore, DRAIC is of great clinical significance in human disease. In this review, we discuss the expression signature, clinical characteristics, biological functions, relevant mechanisms, and potential clinical applications of DRAIC in several human diseases.
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Affiliation(s)
- Qinfan Yao
- Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, China
- National Key Clinical Department of Kidney Diseases, Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Xiuyuan Zhang
- Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, China
- National Key Clinical Department of Kidney Diseases, Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
| | - Dajin Chen
- Kidney Disease Center, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
- Key Laboratory of Kidney Disease Prevention and Control Technology, Hangzhou, China
- National Key Clinical Department of Kidney Diseases, Institute of Nephrology, Zhejiang University, Hangzhou, China
- Zhejiang Clinical Research Center of Kidney and Urinary System Disease, Hangzhou, China
- *Correspondence: Dajin Chen,
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lncRNA LUCAT1/ELAVL1/LIN28B/SOX2 Positive Feedback Loop Promotes Cell Stemness in Triple-Negative Breast Cancer. Breast J 2022; 2022:7689718. [PMID: 35711895 PMCID: PMC9187271 DOI: 10.1155/2022/7689718] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2021] [Revised: 02/25/2022] [Accepted: 03/15/2022] [Indexed: 11/17/2022]
Abstract
Background. Triple-negative breast cancer (TNBC), as a subtype of breast cancer (BC), features an aggressive nature. Long noncoding RNAs (lncRNAs) are proved to get involved in the processes of cancers. lncRNA lung cancer associated transcript 1 (LUCAT1) has been reported in multiple cancers. The role of LUCAT1 in TNBC and its latent regulatory mechanism were investigated. Methods. RT-qPCR was performed to examine LUCAT1 expression. Functional experiments were implemented to disclose the role of LUCAT1 in TNBC. The underlying regulatory mechanism of LUCAT1 in TNBC was explored by chromatin immunoprecipitation (ChIP), RNA-binding protein immunoprecipitation (RIP), luciferase reporter, and RNA pull-down assays. Results. LUCAT1 is significantly overexpressed in TNBC cells. LUCAT1 interference impedes cell stemness in TNBC cells. SRY-box transcription factor 2 (SOX2) is an active transcription factor of LUCAT1. LUCAT1 recruits ELAV-like RNA binding protein 1 (ELAVL1) protein to stabilize lin-28 homolog B (LIN28B) mRNA, thereby further modulating SOX2 expression, which forms a positive feedback loop. Conclusion. The lncRNA LUCAT1/ELAVL1/LIN28B/SOX2 positive feedback loop promotes cell stemness in TNBC. The exploration of the mechanisms underlying TNBC stemness might be beneficial to TNBC treatment.
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Moudry P, Chroma K, Bursac S, Volarevic S, Bartek J. RNA-interference screen for p53 regulators unveils a role of WDR75 in ribosome biogenesis. Cell Death Differ 2022; 29:687-696. [PMID: 34611297 PMCID: PMC8901908 DOI: 10.1038/s41418-021-00882-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2021] [Revised: 09/22/2021] [Accepted: 09/24/2021] [Indexed: 01/05/2023] Open
Abstract
Ribosome biogenesis is an essential, energy demanding process whose deregulation has been implicated in cancer, aging, and neurodegeneration. Ribosome biogenesis is therefore under surveillance of pathways including the p53 tumor suppressor. Here, we first performed a high-content siRNA-based screen of 175 human ribosome biogenesis factors, searching for impact on p53. Knock-down of 4 and 35 of these proteins in U2OS cells reduced and increased p53 abundance, respectively, including p53 accumulation after depletion of BYSL, DDX56, and WDR75, the effects of which were validated in several models. Using complementary approaches including subcellular fractionation, we demonstrate that endogenous human WDR75 is a nucleolar protein and immunofluorescence analysis of ectopic GFP-tagged WDR75 shows relocation to nucleolar caps under chemically induced nucleolar stress, along with several canonical nucleolar proteins. Mechanistically, we show that WDR75 is required for pre-rRNA transcription, through supporting the maintenance of physiological levels of RPA194, a key subunit of the RNA polymerase I. Furthermore, WDR75 depletion activated the RPL5/RPL11-dependent p53 stabilization checkpoint, ultimately leading to impaired proliferation and cellular senescence. These findings reveal a crucial positive role of WDR75 in ribosome biogenesis and provide a resource of human ribosomal factors the malfunction of which affects p53.
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Affiliation(s)
- Pavel Moudry
- Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic.
| | - Katarina Chroma
- grid.10979.360000 0001 1245 3953Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic
| | - Sladana Bursac
- grid.22939.330000 0001 2236 1630Department of Molecular Medicine and Biotechnology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Sinisa Volarevic
- grid.22939.330000 0001 2236 1630Department of Molecular Medicine and Biotechnology, Faculty of Medicine, University of Rijeka, Rijeka, Croatia
| | - Jiri Bartek
- Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czech Republic. .,Genome Integrity, Danish Cancer Society Research Center, Copenhagen, Denmark. .,Division of Genome Biology, Department of Medical Biochemistry and Biophysics, Science for Life Laboratory, Karolinska Institute, Stockholm, Sweden.
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Long noncoding RNA LUCAT1 enhances the survival and therapeutic effects of mesenchymal stromal cells post-myocardial infarction. MOLECULAR THERAPY - NUCLEIC ACIDS 2022; 27:412-426. [PMID: 35036054 PMCID: PMC8733180 DOI: 10.1016/j.omtn.2021.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Accepted: 12/09/2021] [Indexed: 11/25/2022]
Abstract
Mesenchymal stromal cell (MSC) transplantation has been a promising therapeutic strategy for repairing heart tissues post-myocardial infarction (MI). Nevertheless, its therapeutic efficacy remains low, which is mainly ascribed to the low viability of transplanted MSCs. Recently, long noncoding RNAs (lncRNAs) have been reported to participate in diverse physiological and pathological processes, but little is known about their role in MSC survival. Using unbiased transcriptome profiling of hypoxia-preconditioned MSCs (HP-MSCs) and normoxic MSCs (N-MSCs), we identified a lncRNA named lung cancer-associated transcript 1 (LUCAT1) under hypoxia. LUCAT1 knockdown reduced the survival of engrafted MSCs and decreased the MSC-based therapeutic potency, as shown by impaired cardiac function, reduced cardiomyocyte survival, and increased fibrosis post-MI. Conversely, LUCAT1 overexpression had the opposite results. Mechanistically, LUCAT1 bound with and recruited jumonji domain-containing 6 (JMJD6) to the promoter of forkhead box Q1 (FOXQ1), which demethylated FOXQ1 at H4R3me2(s) and H3R2me2(a), thus downregulating Bax expression and upregulating Bcl-2 expression to attenuate MSC apoptosis. Therefore, our findings revealed the protective effects of LUCAT1 on MSC apoptosis and demonstrated that the LUCAT1-mediated JMJD6-FOXQ1 pathway might represent a novel target to potentiate the therapeutic effect of MSC-based therapy for ischemic cardiovascular diseases.
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Lin X, Zhuang S, Chen X, Du J, Zhong L, Ding J, Wang L, Yi J, Hu G, Tang G, Luo X, Liu W, Ye F. lncRNA ITGB8-AS1 functions as a ceRNA to promote colorectal cancer growth and migration through integrin-mediated focal adhesion signaling. Mol Ther 2022; 30:688-702. [PMID: 34371180 PMCID: PMC8821934 DOI: 10.1016/j.ymthe.2021.08.011] [Citation(s) in RCA: 86] [Impact Index Per Article: 28.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2020] [Revised: 06/16/2021] [Accepted: 07/20/2021] [Indexed: 02/07/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) play critical roles in tumorigenesis and progression of colorectal cancer (CRC). However, functions of most lncRNAs in CRC and their molecular mechanisms remain uncharacterized. Here we found that lncRNA ITGB8-AS1 was highly expressed in CRC. Knockdown of ITGB8-AS1 suppressed cell proliferation, colony formation, and tumor growth in CRC, suggesting oncogenic roles of ITGB8-AS1. Transcriptomic analysis followed by KEGG analysis revealed that focal adhesion signaling was the most significantly enriched pathway for genes positively regulated by ITGB8-AS1. Consistently, knockdown of ITGB8-AS1 attenuated the phosphorylation of SRC, ERK, and p38 MAPK. Mechanistically, ITGB8-AS1 could sponge miR-33b-5p and let-7c-5p/let-7d-5p to regulate the expression of integrin family genes ITGA3 and ITGB3, respectively, in the cytosol of cells. Targeting ITGB8-AS1 using antisense oligonucleotide (ASO) markedly reduced cell proliferation and tumor growth in CRC, indicating the therapeutic potential of ITGB8-AS1 in CRC. Furthermore, ITGB8-AS1 was easily detected in plasma of CRC patients, which was positively correlated with differentiation and TNM stage, as well as plasma levels of ITGA3 and ITGB3. In conclusion, ITGB8-AS1 functions as a competing endogenous RNA (ceRNA) to regulate cell proliferation and tumor growth of CRC via regulating focal adhesion signaling. Targeting ITGB8-AS1 is effective in suppressing CRC cell growth and tumor growth. Elevated plasma levels of ITGB8-AS1 were detected in advanced-stage CRC. Thus, ITGB8-AS1 could serve as a potential therapeutic target and circulating biomarker in CRC.
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Affiliation(s)
- Xiaoting Lin
- Department of Medical Oncology, Xiamen Key Laboratory of Antitumor Drug Transformation Research, the First Affiliated Hospital of Xiamen University, Xiamen 361003, China,Department of Clinical Medicine, Fujian Medical University, Fuzhou 350122, China
| | - Shiwen Zhuang
- Department of Medical Oncology, Xiamen Key Laboratory of Antitumor Drug Transformation Research, the First Affiliated Hospital of Xiamen University, Xiamen 361003, China,Department of Clinical Medicine, Fujian Medical University, Fuzhou 350122, China
| | - Xue Chen
- Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361104, China
| | - Jun Du
- Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361104, China
| | - Longhua Zhong
- Department of Medical Oncology, Xiamen Key Laboratory of Antitumor Drug Transformation Research, the First Affiliated Hospital of Xiamen University, Xiamen 361003, China
| | - Jiancheng Ding
- Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361104, China
| | - Lei Wang
- Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361104, China
| | - Jia Yi
- Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361104, China
| | - Guosheng Hu
- Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361104, China
| | - Guohui Tang
- Department of Anus and Bowels, Affiliated Nanhua Hospital, University of South China, Hengyang 421010, China
| | - Xi Luo
- BE/Phase I Clinical Center, First Affiliated Hospital of Xiamen University, Xiamen 361003 China,Corresponding author: Xi Luo, BE/Phase I Clinical Center, First Affiliated Hospital of Xiamen University, Xiamen 361003 China.
| | - Wen Liu
- Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361104, China,Corresponding author: Wen Liu, Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361104, China.
| | - Feng Ye
- Department of Medical Oncology, Xiamen Key Laboratory of Antitumor Drug Transformation Research, the First Affiliated Hospital of Xiamen University, Xiamen 361003, China,Department of Clinical Medicine, Fujian Medical University, Fuzhou 350122, China,Corresponding author: Feng Ye, Department of Clinical Medicine, Fujian Medical University, Fuzhou 350122, China.
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Zheng D, Cao M, Zuo S, Xia X, Zhi C, Lin Y, Deng S, Yuan X. RANBP1 promotes colorectal cancer progression by regulating pre-miRNA nuclear export via a positive feedback loop with YAP. Oncogene 2022; 41:930-942. [PMID: 34615998 DOI: 10.1038/s41388-021-02036-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 09/05/2021] [Accepted: 09/22/2021] [Indexed: 12/20/2022]
Abstract
Colorectal cancer (CRC) is among the top five most common malignant tumors worldwide and has a high mortality rate. Identification of the mechanism of CRC and potential therapeutic targets is critical for improving survival. In the present study, we observed high expression of RAN binding protein 1 (RANBP1) in CRC tissues. Upregulated RANBP1 expression was strongly associated with TNM stages and was an independent risk factor for poor prognosis. In vitro and in vivo functional experiments demonstrated that RANBP1 promoted the proliferation and invasion of CRC cells and inhibited the apoptosis of CRC cells. Low RANBP1 expression reduced the expression levels of hsa-miR-18a, hsa-miR-183, and hsa-miR-106 microRNAs (miRNAs) by inhibiting the nucleoplasmic transport of precursor miRNAs (pre-miRNAs), thereby promoting the accumulation of the latter in the nucleus and reducing the expression of mature miRNAs. Further experiments and bioinformatic analyses demonstrated that RANBP1 promoted the expression of YAP by regulating miRNAs and the Hippo pathway. We also found that YAP acted as a transcriptional cofactor to activate RANBP1 transcription in combination with TEAD4 transcription factor. Thus, RANBP1 further promoted the progression of CRC by forming a positive feedback loop with YAP. Our results revealed the biological role and mechanism of RANBP1 in CRC for the first time, suggesting that RANBP1 can be used as a diagnostic molecule and a potential therapeutic target in CRC.
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Affiliation(s)
- Dandan Zheng
- Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, 211166, China
| | - Meng Cao
- Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China
| | - Siyu Zuo
- Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, 211166, China
- The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, 310003, China
| | - Xin Xia
- Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, 211166, China
| | - Chunchun Zhi
- Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China
| | - Yanbing Lin
- Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, 211166, China
| | - Sitong Deng
- Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, 211166, China
| | - Xiaoqin Yuan
- Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, 211166, China.
- Key Laboratory for Aging & Disease, Nanjing Medical University, Nanjing, 211166, China.
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Shu X, Zhang Z, Yao ZY, Xing XL. Identification of Five Ferroptosis-Related LncRNAs as Novel Prognosis and Diagnosis Signatures for Renal Cancer. Front Mol Biosci 2022; 8:763697. [PMID: 35118117 PMCID: PMC8804361 DOI: 10.3389/fmolb.2021.763697] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Accepted: 12/02/2021] [Indexed: 12/15/2022] Open
Abstract
Background: Ferroptosis is a novel regulated cell death that is characterized by iron-dependent oxidative damage. Renal cancer is the second most common cancer of the urinary system, which is highly correlated with iron metabolism. The aim of our present study was to identify suitable ferroptosis-related prognosis signatures for renal cancer.Methods: We downloaded the RNA-seq count data of renal cancer from The Cancer Genome Atlas database and used the DESeq2, Survival, and Cox regression analyses to screen the prognosis signatures.Results: We identified 5 ferroptosis-related differentially expressed lncRNAs (FR-DELs) (DOCK8-AS1, SNHG17, RUSC1-AS1, LINC02609, and LUCAT1) to be independently correlated with the overall survival (OS) of patients with renal cancer. The risk assessment model and diagnosis model constructed by those 5 FR-DELs could well predict the outcome and the diagnosis of renal cancer.Conclusion: Our present study not only suggested those 5 FR-DELs could be used as prognosis and diagnosis signatures for renal cancer but also provided strategies for other cancers in the screening of ferroptosis-related biomarkers.
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Affiliation(s)
- Xiangjun Shu
- School of Public Health and Laboratory Medicine, Hunan University of Medicine, Huaihua, China
- The First Affiliated Hospital, Hunan University of Medicine, Huaihua, China
| | - Zaiqi Zhang
- The First Affiliated Hospital, Hunan University of Medicine, Huaihua, China
| | - Zhi-Yong Yao
- The First Affiliated Hospital, Hunan University of Medicine, Huaihua, China
| | - Xiao-Liang Xing
- School of Public Health and Laboratory Medicine, Hunan University of Medicine, Huaihua, China
- The First Affiliated Hospital, Hunan University of Medicine, Huaihua, China
- *Correspondence: Xiao-Liang Xing,
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Qiu-Yue X, Tian-Yuan Y, Xiao-Long W, Dong-Mei Q, Xiao-Rui C. Effects of Metformin on Modulating the Expression of Brain-related Genes of APP/PS1 Transgenic Mice based on Single Cell Sequencing. Curr Alzheimer Res 2022; 19:754-771. [PMID: 36464874 DOI: 10.2174/1567205020666221201143323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 10/26/2022] [Accepted: 11/12/2022] [Indexed: 12/07/2022]
Abstract
BACKGROUND Alzheimer's disease is the most common form of dementia, affecting millions of people worldwide. METHODS Here, we analyzed the effects of metformin on APP/PS1 transgenic mice by behavioral test and single-cell sequencing. RESULTS It showed that metformin can improve the spatial learning, memory function, and anxiety mood of APP/PS1 transgenic mice. We identified transcriptionally distinct subpopulations of nine major brain cell types. Metformin increased the differentiation of stem cells, decreased the proportion of cells in the G2 phase, enhanced the generation of neural stem cells and oligodendrocyte progenitor cells, and the tendency of neural stem cells to differentiate into astrocytes. Notably, 253 genes expressed abnormally in APP/PS1 transgenic mice and were reversed by metformin. Ttr, Uba52, and Rps21 are the top 3 genes in the cell-gene network with the highest node degree. Moreover, histochemistry showed the expressions of RPS15, Uba52, and RPL23a were consistent with the data from single-cell sequencing. Pathway and biological process enrichment analysis indicated metformin was involved in nervous system development and negative regulation of the apoptotic process. CONCLUSION Overall, metformin might play an important role in the differentiation and development and apoptotic process of the central nervous system by regulating the expression of Ttr, Uba52, Rps21, and other genes to improve cognition of APP/PS1 transgenic mice. These results provided a clue for elaborating on the molecular and cellular basis of metformin on AD.
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Affiliation(s)
- Xiao Qiu-Yue
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Ye Tian-Yuan
- Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Wang Xiao-Long
- Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Qi Dong-Mei
- Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
| | - Cheng Xiao-Rui
- Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
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Chen Y, Long W, Yang L, Zhao Y, Wu X, Li M, Du F, Chen Y, Yang Z, Wen Q, Yi T, Xiao Z, Shen J. Functional Peptides Encoded by Long Non-Coding RNAs in Gastrointestinal Cancer. Front Oncol 2021; 11:777374. [PMID: 34888249 PMCID: PMC8649637 DOI: 10.3389/fonc.2021.777374] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 10/28/2021] [Indexed: 12/11/2022] Open
Abstract
Gastrointestinal cancer is by far the most common malignancy and the most common cause of cancer-related deaths worldwide. Recent studies have shown that long non-coding RNAs (lncRNAs) play an important role in the epigenetic regulation of cancer cells and regulate tumor progression by affecting chromatin modifications, gene transcription, translation, and sponge to miRNAs. In particular, lncRNA has recently been found to possess open reading frame (ORF), which can encode functional small peptides or proteins. These peptides interact with its targets to regulate transcription or the signal axis, thus promoting or inhibiting the occurrence and development of tumors. In this review, we summarize the involvement of lncRNAs and the function of lncRNAs encoded small peptides in gastrointestinal cancer.
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Affiliation(s)
- Yao Chen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
- Laboratory of Personalised Cell Therapy & Cell Medicines, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Weili Long
- School of Basic Medicine, Southwest Medical University, Luzhou, China
| | - Liqiong Yang
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
- Laboratory of Personalised Cell Therapy & Cell Medicines, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Yueshui Zhao
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
- Laboratory of Personalised Cell Therapy & Cell Medicines, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Xu Wu
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
- Laboratory of Personalised Cell Therapy & Cell Medicines, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Mingxing Li
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
- Laboratory of Personalised Cell Therapy & Cell Medicines, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Fukuan Du
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
- Laboratory of Personalised Cell Therapy & Cell Medicines, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Yu Chen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
- Laboratory of Personalised Cell Therapy & Cell Medicines, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Zhihui Yang
- Department of Pathology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Qinglian Wen
- Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Tao Yi
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, Hong Kong SAR, China
| | - Zhangang Xiao
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
- Laboratory of Personalised Cell Therapy & Cell Medicines, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Jing Shen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- South Sichuan Institute of Translational Medicine, Luzhou, China
- Laboratory of Personalised Cell Therapy & Cell Medicines, School of Pharmacy, Southwest Medical University, Luzhou, China
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Wang X, Tang W, Lu Y, You J, Han Y, Zheng Y. Prognostic Significance of Alternative Splicing Genes in Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma. Int J Gen Med 2021; 14:7933-7949. [PMID: 34785939 PMCID: PMC8590485 DOI: 10.2147/ijgm.s335475] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 10/20/2021] [Indexed: 01/16/2023] Open
Abstract
Background Alternative splicing (AS) acts on many tumors and its relationship with cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) needs to be researched. Methods RNA sequencing data and clinical information of CESC cohorts were obtained from the Cancer Genome Atlas (TCGA) and SpliceSeq was used to analyze the splicing profile of mRNA in CESC. UpSetR displayed the intersections among AS events and univariate analysis chose survival-associated AS and splicing factor (SF) genes. Functional analysis was operated on Enrichr, STRING database and MCODE analysis were used to evaluate protein-protein interaction (PPI) information. LASSO and multivariate analysis constructed prognostic model and risk analysis of tumor infiltrating immune cells was also conducted. Results A total of 402 AS-generated genes were found to be associated with CESC prognosis. Functional analysis showed that Golgi to lysosome transport was enriched. PPI network suggested that UBA52 was most functional. Dendritic cells activated, dendritic cells resting, macrophages M0, mast cells resting, T cells CD4 memory activated and T cells CD8 were most correlative with the risk score. Conclusion SFs and AS events can directly or indirectly affect the prognosis of CESC patients and this study identified SNRPA and CELF2 as two CESC-engaged SFs.
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Affiliation(s)
- Xiaoyu Wang
- Department of Obstetrics and Gynecology, Nantong First People's Hospital, Nantong, Jiangsu, 226001, People's Republic of China
| | - Weichun Tang
- Department of Obstetrics and Gynecology, Nantong First People's Hospital, Nantong, Jiangsu, 226001, People's Republic of China
| | - Yilin Lu
- Department of Obstetrics and Gynecology, Nantong First People's Hospital, Nantong, Jiangsu, 226001, People's Republic of China
| | - Jun You
- Department of Obstetrics and Gynecology, Nantong First People's Hospital, Nantong, Jiangsu, 226001, People's Republic of China
| | - Yun Han
- Department of Obstetrics and Gynecology, Nantong First People's Hospital, Nantong, Jiangsu, 226001, People's Republic of China
| | - Yanli Zheng
- Department of Obstetrics and Gynecology, Nantong First People's Hospital, Nantong, Jiangsu, 226001, People's Republic of China
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Lu Q, Lou J, Cai R, Han W, Pan H. Emerging roles of a pivotal lncRNA SBF2-AS1 in cancers. Cancer Cell Int 2021; 21:417. [PMID: 34372871 PMCID: PMC8351094 DOI: 10.1186/s12935-021-02123-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2021] [Accepted: 07/29/2021] [Indexed: 12/25/2022] Open
Abstract
Long non-coding RNAs refer to transcripts over 200 nt in length that lack the ability to encode proteins, which occupy the majority of the genome and play a crucial role in the occurrence and development of human diseases, especially cancers. SBF2-AS1, a newly identified long non-coding RNA, has been verified to be highly expressed in diversiform cancers, and is involved in processes promoting tumorigenesis, tumor progression and tumor metastasis. Moreover, upregulation of SBF2-AS1 expression was significantly related to disadvantageous clinicopathologic characteristics and indicated poor prognosis. In this review, we comprehensively summarize the up-to-date knowledge of the detailed mechanisms and underlying functions of SBF2-AS1 in diverse cancer types, highlighting the potential of SBF2-AS1 as a diagnostic and prognostic biomarker and even a therapeutic target.
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Affiliation(s)
- Qian Lu
- Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jun Lou
- Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Ruyun Cai
- Department of Colorectal Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Weidong Han
- Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
| | - Hongming Pan
- Department of Medical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
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Zhao S, Lin C, Yang T, Qian X, Lu J, Cheng J. Expression of long non-coding RNA LUCAT1 in patients with chronic obstructive pulmonary disease and its potential functions in regulating cigarette smoke extract-induced 16HBE cell proliferation and apoptosis. J Clin Lab Anal 2021; 35:e23823. [PMID: 34125980 PMCID: PMC8274995 DOI: 10.1002/jcla.23823] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 03/26/2021] [Accepted: 04/10/2021] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Chronic obstructive pulmonary disease (COPD), characterized by persistent airflow limitation, was a disease mediated by a combination of inflammatory factors, immune cells, and immune mediators. COPD was an inflammatory and autoimmune disease involving T-lymphocytes triggered by cigarette smoke and other factors that progressively affected the bronchi, lung parenchyma, and pulmonary blood vessels. LncRNAs were reported to be implicated in COPD pathogenesis and development. METHODS Non-smokers, smokers (non-COPD), and COPD patients were randomly selected in an established COPD surveillance cohort. Demographic and clinical information of all subjects were collected. Pulmonary function was measured by post-bronchodilator testing. qRT-PCR and ELISA assays were performed to detect the expression levels of lncRNA LUCAT1, miR-181a-5p, and inflammatory cytokines. An in vitro exposure model was constructed using cigarette smoke extract (CSE)-induced human bronchial epithelial (16HBE) cells. The dual-luciferase reporter and RNA pull-down assays were used to detect the binding relationship between lncRNA LUCAT1 and miR-181a-5p; meanwhile, Spearman's correlation assay was used to verify the correlation between lncRNA LUCAT1 and miR-181a-5p. Afterward, the lncRNA LUCAT1 silencing plasmid was constructed and co-transfected with a miR-181a-5p inhibitor to evaluate the effects on CSE-induced 16HBE cell proliferation and apoptosis. Finally, a Western blot assay was utilized to determine the mechanism of lncRNA LUCAT1/miR-181a-5p/Wnt/β-catenin axis in COPD. RESULTS LncRNA LUCAT1 was upregulated in the serums of COPD patients. Correlation analysis further confirmed the strong correlation between LUCAT1 expression and inflammatory cytokines IL-1β, IL-6, and TNF-α. Receiver operating characteristic (ROC) analysis verified the potential of LUCAT1 in COPD diagnosis. After treatment with CSE, LUCAT1 was significantly increased while its target miR-181a-5p was decreased in 16HBE cells. Cell proliferation and apoptosis assays showed that LUCAT1 silencing alleviated CSE's effects on 16HBE cell proliferation and apoptosis. Mechanically, rescue assays demonstrated that miR-181a-5p inhibition could partially counteract the impact of LUCAT1 on COPD progression through the Wnt/β-catenin pathway. CONCLUSIONS LncRNA LUCAT1 may be a valuable indicator for differentiating COPD. Moreover, LncRNA LUCAT1/miR-181-5p/Wnt/β-catenin axis behaved as a critical role in COPD development, shedding new sights for clinical treatment.
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Affiliation(s)
- Shan Zhao
- Department of Clinical Laboratory, Affiliated Yixing People's Hospital, Jiangsu University, Wuxi, China
| | - Chunyan Lin
- Department of Blood Transfusion, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Tao Yang
- Department of Clinical Laboratory, Affiliated Yixing People's Hospital, Jiangsu University, Wuxi, China
| | - Xiaoyu Qian
- Department of Clinical Laboratory, Affiliated Yixing People's Hospital, Jiangsu University, Wuxi, China
| | - Junjie Lu
- Department of Critical Care Medicine, Affiliated Yixing People's Hospital, Jiangsu University, Wuxi, China
| | - Jing Cheng
- Department of Blood Transfusion, The First Affiliated Hospital of Soochow University, Suzhou, China
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Cao M, Wang Y, Xiao Y, Zheng D, Zhi C, Xia X, Yuan X. Activation of the clock gene TIMELESS by H3k27 acetylation promotes colorectal cancer tumorigenesis by binding to Myosin-9. J Exp Clin Cancer Res 2021; 40:162. [PMID: 33971927 PMCID: PMC8108341 DOI: 10.1186/s13046-021-01936-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 04/03/2021] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is a common tumor characterized by its high mortality. However, the underlying molecular mechanisms that drive CRC tumorigenesis are unclear. Clock genes have important roles in tumor development. In the present study, the expression and functions of clock gene TIMELESS (encoding the Timeless protein) in CRC were investigated. METHODS Immunohistochemistry, cell proliferation, migration, invasion, EMT and xenograft tumor experiments were used to prove the function of Timeless in the tumorigenesis of CRC. Immunoprecipitation, mass spectrometry, Immunofluorescence and Chromatin immunoprecipitation (ChIP) were utilized to clarify the mechanism of Timeless in regulating CRC tumorigenesis. RESULTS We found that Timeless was upregulated in CRC tissues compared with corresponding normal tissues and its expression was closely associated with the TNM stages and overall survival of CRC patients. Functional studies demonstrated that Timeless promoted the proliferation, invasion, and EMT of CRC cells in vitro and in vivo. Mechanistic investigations showed that Timeless activated the β-catenin signal pathway by binding to Myosin-9, which binds to β-catenin to induce its nuclear translocation. The upregulation of Timeless was attributed to CREB-binding protein (CBP)/p300-mediated H3K27 acetylation of the promoter region of Timeless. CONCLUSION Timeless regulates the tumorigenesis of CRC by binding to and regulating myosin-9, suggesting Timeless might be a potential prognostic biomarker and therapeutic target for CRC.
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Affiliation(s)
- Meng Cao
- Department of General Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, China
| | - Yi Wang
- Department of Anatomy, Histology and Embryology, Nanjing Medical University, Xuehai Building, Rm D509, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China
| | - Yijing Xiao
- Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, 210029, China
| | - Dandan Zheng
- Department of Anatomy, Histology and Embryology, Nanjing Medical University, Xuehai Building, Rm D509, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China
| | - Chunchun Zhi
- Department of Pathology, Nanjing Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, China
| | - Xin Xia
- Department of Anatomy, Histology and Embryology, Nanjing Medical University, Xuehai Building, Rm D509, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China
| | - Xiaoqin Yuan
- Department of Anatomy, Histology and Embryology, Nanjing Medical University, Xuehai Building, Rm D509, 101 Longmian Avenue, Jiangning District, Nanjing, 211166, China.
- Key Laboratory for Aging & Disease, Nanjing Medical University, Nanjing, 211166, China.
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Yang Y, Yan X, Li X, Ma Y, Goel A. Long non-coding RNAs in colorectal cancer: Novel oncogenic mechanisms and promising clinical applications. Cancer Lett 2021; 504:67-80. [PMID: 33577977 PMCID: PMC9715275 DOI: 10.1016/j.canlet.2021.01.009] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 12/29/2020] [Accepted: 01/08/2021] [Indexed: 02/05/2023]
Abstract
Colorectal cancer (CRC) is the third most common malignancy and ranks as the second leading cause of cancer-related deaths worldwide. Despite the improvements in CRC diagnosis and treatment approaches, a considerable proportion of CRC patients still suffers from poor prognosis due to late disease detections and lack of personalized disease managements. Recent evidences have not only provided important molecular insights into their mechanistic behaviors but also indicated that identification of cancer-specific long non-coding RNAs (LncRNAs) could benefit earlier disease detections and improve treatment outcomes in patients suffering from CRC. LncRNAs have raised extensive attentions as they participate in various hallmarks of CRC. The mechanistic evidence gleaned in the recent decade clearly reveals that lncRNAs exert their oncogenic roles by regulating autophagy, epigenetic modifications, enhancing stem phenotype and modifying tumor microenvironment. In view of their pleiotropic functional roles in malignant progression, and their frequently dysregulated expression in CRC patients, they have great potential to be reliable diagnostic and prognostic biomarkers, as well as therapeutic targets for CRC. In the present review, we will focus on the oncogenic roles of lncRNAs and related mechanisms in CRC as well as discuss their clinical potential in the early diagnosis, prognostic prediction and therapeutic translation in patients with this malignancy.
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Affiliation(s)
- Yufei Yang
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xuebing Yan
- Department of Oncology, Affiliated Hospital of Yangzhou University, Yangzhou, China
| | - Xinxiang Li
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Yanlei Ma
- Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
| | - Ajay Goel
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
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Study of the biological function of LncRNA LUCAT1 on cervical cancer cells by targeting miR-199b-5p. Biosci Rep 2021; 40:222453. [PMID: 32207530 PMCID: PMC7178215 DOI: 10.1042/bsr20200422] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2020] [Revised: 02/26/2020] [Accepted: 02/27/2020] [Indexed: 12/16/2022] Open
Abstract
To explore the effect and mechanism of LncRNA LUCAT1 in cervical cancer (CC). In the present study, 67 cases of CC patients and 60 healthy cases were selected as the research objects. CC patients were selected as the study group (SG) and healthy physical examination patients were selected as the control group (CG). LUCAT1 expression level in peripheral blood was detected in the two groups. Human cervical carcinoma cells C33A, AV3 and normal cervical epithelial cells H8 were purchased for biological behavior analysis. LUCAT1 was highly expressed in SG and cancer tissues (P<0.050), and it had good diagnostic value for the development of CC (P<0.001). It was closely related to the differentiation, pathological stage and metastasis of CC (P<0.001). The prognosis of CC patients was affected (P<0.050). After transfecting LUCAT1 into CC cells, it was found that the proliferation, invasion ability and anti-apoptosis protein of CC cells were significantly reduced, while the apoptosis rate and apoptosis protein were significantly increased by inhibiting LUCAT1 expression (P<0.050). However, after transfecting miR-199b-5p into CC cells, it was found that the proliferation, invasion ability and anti-apoptosis protein of CC cells were significantly increased, while the apoptosis rate and apoptosis protein were significantly decreased by inhibiting LUCAT1 expression (P<0.050). LUCAT1 was highly expressed in CC. It was involved in the tumor development of CC by targeting miR-199b-5p, which was of great significance for the diagnosis and treatment of CC in the future.
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Liao Z, Nie H, Wang Y, Luo J, Zhou J, Ou C. The Emerging Landscape of Long Non-Coding RNAs in Colorectal Cancer Metastasis. Front Oncol 2021; 11:641343. [PMID: 33718238 PMCID: PMC7947863 DOI: 10.3389/fonc.2021.641343] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 01/29/2021] [Indexed: 12/11/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common gastrointestinal cancers, with extremely high rates of morbidity and mortality. The main cause of death in CRC is distant metastasis; it affects patient prognosis and survival and is one of the key challenges in the treatment of CRC. Long non-coding RNAs (lncRNAs) are a group of non-coding RNA molecules with more than 200 nucleotides. Abnormal lncRNA expression is closely related to the occurrence and progression of several diseases, including cancer. Recent studies have shown that numerous lncRNAs play pivotal roles in the CRC metastasis, and reversing the expression of these lncRNAs through artificial means can reduce the malignant phenotype of metastatic CRC to some extent. This review summarizes the major mechanisms of lncRNAs in CRC metastasis and proposes lncRNAs as potential therapeutic targets for CRC and molecular markers for early diagnosis.
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Affiliation(s)
- Zhiming Liao
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
| | - Hui Nie
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
| | - Yutong Wang
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
| | - Jingjing Luo
- Teaching and Research Room of Biochemistry and Molecular Biology, Medical School of Hunan University of Traditional Chinese Medicine, Changsha, China
| | - Jianhua Zhou
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Chunlin Ou
- Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
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Ma M, Li L, Long F, Xiao H, Lu M, Lin C. MiR-133b inhibits colorectal cancer metastasis via lncRNA-LUCAT1. Future Oncol 2021; 17:1013-1023. [PMID: 33541136 DOI: 10.2217/fon-2020-0420] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Aim: Colorectal cancer (CRC) is a common malignant tumor of the digestive system. Metastasis is the leading cause of poor prognosis of CRC patients, warranting further study of the molecular mechanism of metastasis in CRC and identification of new therapeutic targets. MiR-133b has been proven to play an important role in tumorigenesis by directly targeting coding genes. However, whether miR-133b can regulate tumorigenesis via long noncoding RNA (lncRNA) remains unclear. Methods: We systematically analyzed the expression level and correlation of miR-133b and LUCAT1 in cancer tissues and adjacent tissues from 30 patients with CRC. The effects of miR-133b and LUCAT1 on the invasive ability of CRC cells were detected by a transwell assay. The relationship between miR-133b and LUCAT1 was investigated by cells transfection experiments, rescue experiments and luciferase reporter assays. The binding of LUCAT1 and EZH2 was detected by RNA immunoprecipitation assay. Results: MiR-133b was expressed at low levels in CRC tissues, and LUCAT1 was highly expressed, with an inverse correlation between them. LUCAT1 promoted the migration and invasion of HCT116 and SW620 cells. Overexpression of LUCAT1 attenuated the inhibition of cell migration and invasion induced by miR-133b. However, the dual luciferase assay showed that miR-133b did not directly target LUCAT1. Conclusion: MiR-133b affects CRC metastasis via the LUCAT1/EZH2 complex. MiR-133b and LUCAT1 may be potential targets for antimetastasis therapy in CRC.
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Affiliation(s)
- Min Ma
- Postdoctoral Research Station of Clinical Medicine, The Third Xiangya Hospital of Central South University, Changsha, 410013, China.,Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, 410013, China
| | - Liang Li
- Clinical School of Medicine, University of South China, Hengyang, 421000, China
| | - Fei Long
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, 410013, China
| | - Hua Xiao
- Department of Hepatobiliary & Intestinal Surgery, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410013, China
| | - Min Lu
- Department of Oncology, The Second Xiangya Hospital, Central South University, Changsha, 410011, China
| | - Changwei Lin
- Department of Gastrointestinal Surgery, The Third Xiangya Hospital of Central South University, Changsha, 410013, China
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Xing C, Sun SG, Yue ZQ, Bai F. Role of lncRNA LUCAT1 in cancer. Biomed Pharmacother 2020; 134:111158. [PMID: 33360049 DOI: 10.1016/j.biopha.2020.111158] [Citation(s) in RCA: 201] [Impact Index Per Article: 40.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2020] [Revised: 12/03/2020] [Accepted: 12/14/2020] [Indexed: 02/09/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) are RNA molecules with a transcript length of more than 200 nt and lack a protein-coding ability. They regulate gene expression by interacting with protein, RNA, and DNA. Their function is closely related to their subcellular localization. In the nucleus, lncRNAs regulate gene expression at the epigenetic and transcriptional levels, and in the cytoplasm, they regulate gene expression at the post-transcriptional and translational levels. Abnormalities in lncRNAs have been confirmed to exhibit tumor suppressor or carcinogenic effects and play an important role in the development of tumors. In particular, the lung cancer-related transcript 1 (LUCAT1) located in the antisense strand of the q14.3 region of chromosome 5 was first discovered in smoking-related lung cancer. Increasing evidence have showed that LUCAT1 is involved in breast cancer, ovarian cancer, thyroid cancer, renal cell carcinoma. It is highly expressed in liver cancer and other malignant tumors and has been confirmed to be induce various malignant tumors. It regulates tumor proliferation, invasion, and migration via various mechanisms and is related to the clinicopathological characteristics of tumor patients. Thus, LUCAT1 is a potential prognostic biological marker and therapeutic target for cancer. This article reviews its expression, function, and molecular mechanism in various malignant tumors.
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Affiliation(s)
- Ce Xing
- Lanzhou University Second Hospital, Department of Cardiology, 82 Cuiying Men, Lanzhou, 730030, PR China
| | - Shou-Gang Sun
- Lanzhou University Second Hospital, Department of Cardiology, 82 Cuiying Men, Lanzhou, 730030, PR China
| | - Zhi-Quan Yue
- Lanzhou University Second Hospital, Department of Cardiology, 82 Cuiying Men, Lanzhou, 730030, PR China
| | - Feng Bai
- Lanzhou University Second Hospital, Department of Cardiology, 82 Cuiying Men, Lanzhou, 730030, PR China.
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Agarwal S, Vierbuchen T, Ghosh S, Chan J, Jiang Z, Kandasamy RK, Ricci E, Fitzgerald KA. The long non-coding RNA LUCAT1 is a negative feedback regulator of interferon responses in humans. Nat Commun 2020; 11:6348. [PMID: 33311506 PMCID: PMC7733444 DOI: 10.1038/s41467-020-20165-5] [Citation(s) in RCA: 52] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Accepted: 11/12/2020] [Indexed: 12/31/2022] Open
Abstract
Long non-coding RNAs are important regulators of biological processes including immune responses. The immunoregulatory functions of lncRNAs have been revealed primarily in murine models with limited understanding of lncRNAs in human immune responses. Here, we identify lncRNA LUCAT1 which is upregulated in human myeloid cells stimulated with lipopolysaccharide and other innate immune stimuli. Targeted deletion of LUCAT1 in myeloid cells increases expression of type I interferon stimulated genes in response to LPS. By contrast, increased LUCAT1 expression results in a reduction of the inducible ISG response. In activated cells, LUCAT1 is enriched in the nucleus where it associates with chromatin. Further, LUCAT1 limits transcription of interferon stimulated genes by interacting with STAT1 in the nucleus. Together, our study highlights the role of the lncRNA LUCAT1 as a post-induction feedback regulator which functions to restrain the immune response in human cells.
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Affiliation(s)
- Shiuli Agarwal
- Program in Innate Immunity, University of Massachusetts Medical School, Worcester, MA, 01605, USA
| | - Tim Vierbuchen
- Program in Innate Immunity, University of Massachusetts Medical School, Worcester, MA, 01605, USA
| | - Sreya Ghosh
- Program in Innate Immunity, University of Massachusetts Medical School, Worcester, MA, 01605, USA
| | - Jennie Chan
- Program in Innate Immunity, University of Massachusetts Medical School, Worcester, MA, 01605, USA
| | - Zhaozhao Jiang
- Program in Innate Immunity, University of Massachusetts Medical School, Worcester, MA, 01605, USA
| | - Richard K Kandasamy
- Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7491, Trondheim, Norway
| | - Emiliano Ricci
- Université de Lyon, ENSL, UCBL, CNRS, INSERM, LBMC, 46 Allée d'Italie, 69007, Lyon, France
| | - Katherine A Fitzgerald
- Program in Innate Immunity, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
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Zhao Z, Xing Y, Liu Y, Jing S. Lung cancer‑associated transcript 1 facilitates tumorigenesis in laryngeal squamous cell carcinoma through the targeted inhibition of miR‑493. Mol Med Rep 2020; 23:59. [PMID: 33215214 PMCID: PMC7705996 DOI: 10.3892/mmr.2020.11697] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Accepted: 07/07/2020] [Indexed: 12/19/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) serve important roles in the tumorigenesis of a diverse range of cancer types. The lung cancer-associated transcript 1 (LUCAT1), has been reported to promote the proliferation, migration and invasion of oral squamous cell carcinoma cells. However, the exact role of LUCAT1 in laryngeal squamous cell carcinoma (LSCC) remains to fully understood. The present study aimed to interrogate the role and modulatory mechanism of LUCAT1 in LSCC. Reverse transcription-quantitative PCR and western blotting were used to investigate the expression of LUCAT1 and miR-493, as well as the protein expression of cyclin-dependent kinase 2, cyclin E1, p21, matrix metalloproteinase (MMP)2, MMP9, vascular endothelial growth factor-C, Bcl-2, Bax, cleaved caspase-3 and procaspase-3. Cell Counting Kit-8, flow cytometry, wound healing and Transwell assays were performed to analyze the proliferation, cell cycle, apoptosis levels, and the migratory and invasive abilities, respectively, of the LSCC AMC-HN-8 cell line. In addition, dual-luciferase reporter and ribonucleoprotein immunoprecipitation assays were used to investigate the binding between LUCAT1 and microRNA (miR)-493. The results of the present study revealed that the expression levels of LUCAT1 were upregulated in AMC-HN-8 cells. The genetic knockdown of LUCAT1 expression levels significantly suppressed the cell proliferation, alongside downregulating the expression levels of CDK2 and cyclin E1 and upregulating p21 expression levels. In addition, the knockdown of LUCAT1 inhibited cell migration and invasion, as demonstrated using the wound healing and Transwell assays, respectively. Moreover, LUCAT1 knockdown promoted cell apoptosis and upregulated the expression levels of Bax and cleaved caspase-3, whilst downregulating the expression levels of Bcl-2. Furthermore, LUCAT1 was discovered to directly bind to and inhibit the well-known tumor suppressor, miR-493. Notably, the specific inhibition of miR-493 partly blocked the anticancer effects of LUCAT1 knockdown in AMC-HN-8 cells. In conclusion, these results suggested that LUCAT1 may facilitate tumorigenesis in LSCC through the targeted inhibition of miR-493, which provides evidence for a novel target for the treatment of LSCC.
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Affiliation(s)
- Zhen Zhao
- Department of Otorhinolaryngology‑Head and Neck Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
| | - Yan Xing
- The Third Department of Rehabilitation, Shijiazhuang No. 1 Hospital, Shijiazhuang, Hebei 050000, P.R. China
| | - Yan Liu
- Department of Otorhinolaryngology‑Head and Neck Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
| | - Shanghua Jing
- Department of Otorhinolaryngology‑Head and Neck Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
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Byun HJ, Yoon JH, Lee SK. LUCAT1 Epigenetically Downregulates the Tumor Suppressor Genes CXXC4 and SFRP2 in Gastric Cancer. Yonsei Med J 2020; 61:923-934. [PMID: 33107235 PMCID: PMC7593101 DOI: 10.3349/ymj.2020.61.11.923] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 09/02/2020] [Accepted: 09/03/2020] [Indexed: 12/18/2022] Open
Abstract
PURPOSE The mechanisms of Wnt/β-catenin pathway signaling and abnormal expression of tumor suppressor genes is not well known in gastric cancer (GC). Long non-coding RNA (lncRNA) has recently been identified as a possible link therein. In this study, we investigated the role of lung cancer associated transcript 1 (LUCAT1) in GC. MATERIALS AND METHODS The expression of LUCAT1 in GC cell lines and 100 tissue samples was examined by qRT-PCR. Two different siRNAs were used for knockdown of LUCAT1 expression. Cell viability was assessed by MTT assay. To analyze metastasis, scratch wound-healing assay, a Matrigel invasion assay, and colony formation assay were performed. Apoptosis was analyzed by PI/Annexin-V staining. To check the methylation status in tumor suppressor genes, methylation-specific PCR was carried out. Western blot was performed to detect epithelial-mesenchymal transition and apoptosis markers upon silencing of LUCAT1 (siLUCAT1). RESULTS LUCAT1 expression in GC cell lines and tissues was significantly elevated, compared to that in normal gastric cells and adjacent non-tumor tissues (p<0.001). Two different siRNAs for LUCAT1 reduced cell proliferation, invasion, and migration, compared to siCT (p<0.05), and these reductions were restored by pcDNA-LUCAT1 (p<0.05). siLUCAT1 elicited upregulation of the expression of CXXC4 and SFRP2. The expression of H3K27me3 was reduced by siLUCAT1, and this reduction was correlated with methylation of CXXC4 and SFRP2. Inhibition of LUCAT1 up-regulated EZH2 expression and resulted in demethylation of CXXC4 and SFRP2 through the Wnt/β-catenin signaling pathway. CONCLUSION We concluded that LUCAT1 induces methylation of CXXC4 and SFRP2, thereby regulating Wnt/β-catenin signaling in GC.
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Affiliation(s)
- Hyo Joo Byun
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Korea
| | - Jung Ho Yoon
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
| | - Sang Kil Lee
- Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea
- Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Korea.
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