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Wang J, Liu ZX, Huang ZH, Wen J, Rao ZZ. Long non-coding RNA in the regulation of cell death in hepatocellular carcinoma. World J Clin Oncol 2025; 16:104061. [DOI: 10.5306/wjco.v16.i4.104061] [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: 12/08/2024] [Revised: 02/02/2025] [Accepted: 02/25/2025] [Indexed: 03/26/2025] Open
Abstract
Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer, accounting for 90% of all cases. Currently, early diagnosis of HCC can be achieved through serum alpha-fetoprotein detection, B-ultrasound, and computed tomography scanning; however, their specificity and sensitivity are suboptimal. Despite significant advancements in HCC biomarker detection, the prognosis for patients with HCC remains unfavorable due to tumor heterogeneity and limited understanding of its pathogenesis. Therefore, it is crucial to explore more sensitive HCC biomarkers for improved diagnosis, monitoring, and management of the disease. Long non-coding RNA (lncRNA) serves as an auxiliary carrier of genetic information and also plays diverse intricate regulatory roles that greatly contribute to genome complexity. Moreover, investigating gene expression regulation networks from the perspective of lncRNA may provide insights into the diagnosis and prognosis of HCC. We searched the PubMed database for literature, comprehensively classified regulated cell death mechanisms and systematically reviewed research progress on lncRNA-mediated cell death pathways in HCC cells. Furthermore, we prospectively summarize its potential implications in diagnosing and treating HCC.
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Affiliation(s)
- Jiang Wang
- Children Medical Center, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410013, Hunan Province, China
| | - Zi-Xuan Liu
- Children Medical Center, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410013, Hunan Province, China
| | - Zhi-Hong Huang
- Children Medical Center, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410013, Hunan Province, China
| | - Jie Wen
- Department of Pediatric Orthopedics, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha 410013, Hunan Province, China
| | - Zhou-Zhou Rao
- Department of Physiology, Hunan Normal University School of Medicine, Changsha 410003, Hunan Province, China
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Wang K, Yu J, Xu Q, Peng Y, Li H, Lu Y, Ouyang M. Disulfidptosis-related long non-coding RNA signature predicts the prognosis, tumor microenvironment, immunotherapy, and antitumor drug options in colon adenocarcinoma. Apoptosis 2024; 29:2074-2090. [PMID: 39115621 PMCID: PMC11550253 DOI: 10.1007/s10495-024-02011-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/24/2024] [Indexed: 11/10/2024]
Abstract
This study aims to investigate the role and prognostic significance of long non-coding RNAs (lncRNAs) associated with disulfidptosis in colon adenocarcinoma (COAD). The TCGA database's clinical data and transcriptome profiles were employed. Analysis of previous studies identified 10 disulfidptosis-related genes (DRGs). We used these genes to construct a signature that could independently and accurately predict the prognosis of patients with COAD. The Kaplan-Meier (K-M) curve analysis showed that the lower-risk group had a better prognosis. With the help of multivariate Cox regression analysis, the risk score produced from the patient's signature might independently predict the outcomes. Utilizing a nomogram, the receiver operating characteristic (ROC) curve, and principal component analysis (PCA), the signature's predictive ability was also confirmed. It's interesting to note that immunotherapy, especially PD-1 immune checkpoint suppression, was more likely to benefit low-risk patients. The IC50 levels for certain anticancer agents were lower in the high-risk group. Finally, qRT-PCR analyses in colon cancer cell lines revealed elevated levels of lncRNAs CASC9, ZEB1-AS1, ATP2A1-AS1, SNHG7, AL683813.1, and AP003555.1, and reduced levels of FAM160A1-DT and AC112220.2, compared to normal cell lines. This signature offers insights into prognosis, tumor microenvironment, and options for immunotherapy and antitumor drugs in patients with COAD.
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Affiliation(s)
- Kang Wang
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Shunde, Foshan, Guangdong Province, 528300, China
| | - Jing Yu
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Shunde, Foshan, Guangdong Province, 528300, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, 510080, China
| | - Qihuan Xu
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Shunde, Foshan, Guangdong Province, 528300, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, 510080, China
| | - Yuanhong Peng
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Shunde, Foshan, Guangdong Province, 528300, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, 510080, China
| | - Haibin Li
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Shunde, Foshan, Guangdong Province, 528300, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, 510080, China
| | - Yan Lu
- Guangdong Medical University, Zhanjiang, Dongguan, 523808, China.
- GCP Center, Shunde Hospital, Southern Medical University, The First People's Hospital of Shunde Foshan), Foshan, Guangdong, 528300, China.
| | - Manzhao Ouyang
- Department of Gastrointestinal Surgery, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Shunde, Foshan, Guangdong Province, 528300, China.
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, 510080, China.
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Yu J, He C, Peng Y, Wen Y, Wang J. LncRNA CASC9 facilitates papillary thyroid cancer development and doxorubicin resistance via miR-28-3p/BCL-2 axis and PI3K/AKT signaling pathway. J Cardiothorac Surg 2024; 19:629. [PMID: 39538340 PMCID: PMC11559104 DOI: 10.1186/s13019-024-03129-4] [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: 04/16/2024] [Accepted: 11/02/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Papillary thyroid cancer (PTC) is a malignant tumor that poses a serious threat to human health. LncRNA CASC9 serves as an oncogene in numerous tumors. The purpose of this study was to explore the mechanism of lncRNA CASC9 regulating doxorubicin (Dox) resistance in PTC. METHODS The expression of CASC9, miR-28-3p and BCL-2 in PTC tissues or dox-resistant cells was determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot (WB). CCK-8, colony formation assay, flow cytometry and transwell assay were used to measure the semi-inhibitory concentration (IC50) of dox, cell proliferation, apoptosis and migration, respectively. Dual luciferase reporter gene assays were performed to verify the targeting relationship between miR-28-3p and CASC9 or BCL-2. Rescue experiments were applied to verify the mechanism of CASC9. Finally, the role of CASC9 was verified by xenograft modeling in vivo. RESULTS We discovered that CASC9 was enhanced in PTC tissues, cells and Dox-resistant cells (BCPAP/Dox and K1/Dox). Furthermore, CASC9 inhibition markedly restrained the proliferation, migration and facilitated apoptosis of Dox cells. In vivo experiments also showed that silencing of CASC9 inhibited tumor growth. Meanwhile, knockdown of CASC9 sensitized PTC cells to Dox. CASC9 enhanced tumor progression by activating the PI3K/AKT signaling pathway. Furthermore, bioinformatics analysis identified miR-28-3p as a downstream target of CASC9. MiR-28-3p inhibitor reversed the impact of CASC9 knockdown in BCPAP/Dox and K1/Dox. Further studies showed that CASC9 positively regulated BCL-2 expression through miR-28-3p. miR-28-3p weakened Dox resistance, proliferation, migration and accelerated apoptosis of PTC cells via BCL-2. CONCLUSION CASC9, as an oncogenic lncRNA, has a promotional effect on Dox resistance and PTC progression via miR-28-3p/BCL-2 axis and PI3K/AKT signaling pathway.
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MESH Headings
- Humans
- RNA, Long Noncoding/genetics
- RNA, Long Noncoding/metabolism
- Doxorubicin/pharmacology
- Thyroid Cancer, Papillary/genetics
- Thyroid Cancer, Papillary/metabolism
- Thyroid Cancer, Papillary/pathology
- MicroRNAs/genetics
- MicroRNAs/metabolism
- Drug Resistance, Neoplasm/genetics
- Signal Transduction/drug effects
- Proto-Oncogene Proteins c-akt/metabolism
- Proto-Oncogene Proteins c-akt/genetics
- Thyroid Neoplasms/genetics
- Thyroid Neoplasms/metabolism
- Thyroid Neoplasms/pathology
- Thyroid Neoplasms/drug therapy
- Phosphatidylinositol 3-Kinases/metabolism
- Phosphatidylinositol 3-Kinases/genetics
- Proto-Oncogene Proteins c-bcl-2/genetics
- Proto-Oncogene Proteins c-bcl-2/metabolism
- Mice
- Cell Proliferation/drug effects
- Animals
- Gene Expression Regulation, Neoplastic/drug effects
- Antibiotics, Antineoplastic/pharmacology
- Apoptosis/drug effects
- Cell Line, Tumor
- Mice, Nude
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Affiliation(s)
- Jianping Yu
- Thyroid Surgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, 341000, China
| | - Chun He
- Thyroid Surgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, 341000, China
| | - Yun Peng
- Thyroid Surgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, 341000, China
| | - Yuzhong Wen
- Thyroid Surgery, Ganzhou People's Hospital, Ganzhou, Jiangxi, 341000, China
| | - Jing Wang
- Intensive Care Unit, Ganzhou People's Hospital, No.16 Meiguan Avenue, Zhanggong District, Ganzhou, Jiangxi, 341000, China.
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Jin X, Huang CX, Tian Y. The multifaceted perspectives on the regulation of lncRNAs in hepatocellular carcinoma ferroptosis: from bench-to-bedside. Clin Exp Med 2024; 24:146. [PMID: 38960924 PMCID: PMC11222271 DOI: 10.1007/s10238-024-01418-9] [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: 05/18/2024] [Accepted: 06/24/2024] [Indexed: 07/05/2024]
Abstract
Despite being characterized by high malignancy, high morbidity, and low survival rates, the underlying mechanism of hepatocellular carcinoma (HCC) has not been fully elucidated. Ferroptosis, a non-apoptotic form of regulated cell death, possesses distinct morphological, biochemical, and genetic characteristics compared to other types of cell death. Dysregulated actions within the molecular network that regulates ferroptosis have been identified as significant contributors to the progression of HCC. Long non-coding RNAs (lncRNAs) have emerged as influential contributors to diverse cellular processes, regulating gene function and expression through multiple mechanistic pathways. An increasing body of evidence indicates that deregulated lncRNAs are implicated in regulating malignant events such as cell proliferation, growth, invasion, and metabolism by influencing ferroptosis in HCC. Therefore, elucidating the inherent role of ferroptosis and the modulatory functions of lncRNAs on ferroptosis in HCC might promote the development of novel therapeutic interventions for this disease. This review provides a succinct overview of the roles of ferroptosis and ferroptosis-related lncRNAs in HCC progression and treatment, aiming to drive the development of promising therapeutic targets and biomarkers for HCC patients.
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Affiliation(s)
- Xin Jin
- Department of Gastroenterology and Hepatology, Fengdu People's Hospital, Fengdu County, Chongqing, 408200, China
| | - Chun Xia Huang
- Department of Gastroenterology and Hepatology, Fengdu People's Hospital, Fengdu County, Chongqing, 408200, China
| | - Yue Tian
- Department of Gastroenterology and Hepatology, Fengdu People's Hospital, Fengdu County, Chongqing, 408200, China.
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Ghafouri-Fard S, Askari A, Hussen BM, Taheri M, Akbari Dilmaghani N. Role of miR-424 in the carcinogenesis. Clin Transl Oncol 2024; 26:16-38. [PMID: 37178445 PMCID: PMC10761534 DOI: 10.1007/s12094-023-03209-2] [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: 02/16/2023] [Accepted: 04/27/2023] [Indexed: 05/15/2023]
Abstract
Recent studies have revealed the impact of microRNAs (miRNAs) in the carcinogenic process. miR-424 is a miRNA whose role in this process is being to be identified. Experiments in the ovarian cancer, cervical cancer, hepatocellular carcinoma, neuroblastoma, breast cancer, osteosarcoma, intrahepatic cholangiocarcinoma, prostate cancer, endometrial cancer, non-small cell lung cancer, hemangioma and gastric cancer have reported down-regulation of miR-424. On the other hand, this miRNA has been found to be up-regulated in melanoma, laryngeal and esophageal squamous cell carcinomas, glioma, multiple myeloma and thyroid cancer. Expression of this miRNA is regulated by methylation status of its promoter. Besides, LINC00641, CCAT2, PVT1, LIN00657, LINC00511 and NNT-AS1 are among lncRNAs that act as molecular sponges for miR-424, thus regulating its expression. Moreover, several members of SNHG family of lncRNAs have been found to regulate expression of miR-424. This miRNA is also involved in the regulation of E2F transcription factors. The current review aims at summarization of the role of miR-424 in the process of cancer evolution and its impact on clinical outcome of patients in order to find appropriate markers for malignancies.
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Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Arian Askari
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bashdar Mahmud Hussen
- Department of Clinical Analysis, College of Pharmacy, Hawler Medical University, Kurdistan Region, Erbil, Iraq
| | - Mohammad Taheri
- Institute of Human Genetics, Jena University Hospital, Jena, Germany.
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| | - Nader Akbari Dilmaghani
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Yu H, Liu P, Chen T. CircIFFO1 suppresses tumor growth and metastasis of cutaneous squamous cell carcinoma by targeting the miR-424-5p/NFIB axis. Arch Dermatol Res 2023; 315:2585-2596. [PMID: 37405427 DOI: 10.1007/s00403-023-02659-6] [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: 02/14/2023] [Revised: 03/14/2023] [Accepted: 06/18/2023] [Indexed: 07/06/2023]
Abstract
Cutaneous squamous cell carcinoma (CSCC) is a severe malignancy derived from the skin. Circular RNAs (circRNAs) play an important role in the pathological process of many malignant tumors. Moreover, circIFFO1 is reported to be down-regulated in CSCC tissues compared with non-lesional skin tissues. This study aimed to explore the specific role and potential mechanism of circIFFO1 in CSCC progression. Cell proliferation ability was analyzed by 3-(4, 5-dimethylthiazol-2-y1)-2,5-diphenyl tetrazolium bromide (MTT), 5-ethynyl-2'-deoxyuridine (EdU) incorporation, and colony-formation assays. Cell cycle progression and apoptosis were detected by flow cytometry. Cell migration and invasion were examined by transwell assays. The interaction between microRNA-424-5p (miR-424-5p) and circIFFO1 or nuclear factor I/B (NFIB) was validated by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays. Xenograft tumor assay and immunohistochemistry (IHC) assay were employed to analyze the tumorigenesis in vivo. CircIFFO1 level was down-regulated in CSCC tissues and cell lines. CircIFFO1 overexpression suppressed the proliferation, migration, invasion, and promoted apoptosis of CSCC cells. CircIFFO1 acted as a molecular sponge for miR-424-5p. The anti-tumor effects mediated by circIFFO1 overexpression in CSCC cells could be reversed by miR-424-5p overexpression. miR-424-5p interacted with the 3' untranslated region (3'UTR) of Nuclear Factor I/B (NFIB). miR-424-5p knockdown suppressed the malignant behaviors of CSCC cells, and NFIB knockdown counteracted the anti-tumor effects of miR-424-5p absence in CSCC cells. Additionally, circIFFO1 overexpression restrained xenograft tumor growth in vivo. CircIFFO1 suppressed the malignant behaviors of CSCC by mediating the miR-424-5p/NFIB axis, which provided new insights into the pathogenesis of CSCC.
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Affiliation(s)
- Hui Yu
- Department of Pathology, Huangdao District Central Hospital, Qingdao, China
| | - Penglin Liu
- Department of Anorectal Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Tianli Chen
- Department of Dermatology, Huangdao District Central Hospital, No. 9 Huangpujiang Road, Huangdao District, Qingdao City, 266555, Shandong Province, China.
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7
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Jesenko T, Brezar SK, Cemazar M, Biasin A, Tierno D, Scaggiante B, Grassi M, Grassi C, Dapas B, Truong NH, Abrami M, Zanconati F, Bonazza D, Rizzolio F, Parisi S, Pastorin G, Grassi G. Targeting Non-Coding RNAs for the Development of Novel Hepatocellular Carcinoma Therapeutic Approaches. Pharmaceutics 2023; 15:pharmaceutics15041249. [PMID: 37111734 PMCID: PMC10145575 DOI: 10.3390/pharmaceutics15041249] [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: 03/19/2023] [Revised: 04/12/2023] [Accepted: 04/13/2023] [Indexed: 04/29/2023] Open
Abstract
Hepatocellular carcinoma (HCC) remains a global health challenge, representing the third leading cause of cancer deaths worldwide. Although therapeutic advances have been made in the few last years, the prognosis remains poor. Thus, there is a dire need to develop novel therapeutic strategies. In this regard, two approaches can be considered: (1) the identification of tumor-targeted delivery systems and (2) the targeting of molecule(s) whose aberrant expression is confined to tumor cells. In this work, we focused on the second approach. Among the different kinds of possible target molecules, we discuss the potential therapeutic value of targeting non-coding RNAs (ncRNAs), which include micro interfering RNAs (miRNAs), long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). These molecules represent the most significant RNA transcripts in cells and can regulate many HCC features, including proliferation, apoptosis, invasion and metastasis. In the first part of the review, the main characteristics of HCC and ncRNAs are described. The involvement of ncRNAs in HCC is then presented over five sections: (a) miRNAs, (b) lncRNAs, (c) circRNAs, (d) ncRNAs and drug resistance and (e) ncRNAs and liver fibrosis. Overall, this work provides the reader with the most recent state-of-the-art approaches in this field, highlighting key trends and opportunities for more advanced and efficacious HCC treatments.
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Affiliation(s)
- Tanja Jesenko
- Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana, Slovenia
| | - Simona Kranjc Brezar
- Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana, Slovenia
| | - Maja Cemazar
- Department of Experimental Oncology, Institute of Oncology Ljubljana, Zaloska 2, SI-1000 Ljubljana, Slovenia
- Faculty of Health Sciences, University of Primorska, Polje 42, SI-6310 Izola, Slovenia
| | - Alice Biasin
- Department of Engineering and Architecture, Trieste University, via Valerio 6, I-34127 Trieste, Italy
| | - Domenico Tierno
- Department of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I-34149 Trieste, Italy
| | - Bruna Scaggiante
- Department of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I-34149 Trieste, Italy
| | - Mario Grassi
- Department of Engineering and Architecture, Trieste University, via Valerio 6, I-34127 Trieste, Italy
| | - Chiara Grassi
- Degree Course in Medicine, University of Trieste, I-34149 Trieste, Italy
| | - Barbara Dapas
- Department of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I-34149 Trieste, Italy
| | - Nhung Hai Truong
- Faculty of Biology and Biotechnology, VNUHCM-University of Science, Ho Chi Minh City 70000, Vietnam
| | - Michela Abrami
- Department of Engineering and Architecture, Trieste University, via Valerio 6, I-34127 Trieste, Italy
| | - Fabrizio Zanconati
- Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume, 447, I-34149 Trieste, Italy
| | - Deborah Bonazza
- Department of Medical, Surgical and Health Sciences, University of Trieste, Cattinara Hospital, Strada di Fiume, 447, I-34149 Trieste, Italy
| | - Flavio Rizzolio
- Pathology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, I-33081 Aviano, Italy
- Department of Molecular Sciences and Nanosystems, Ca' Foscari University of Venice, I-30172 Venezia, Italy
| | - Salvatore Parisi
- Department of Molecular Sciences and Nanosystems, Ca' Foscari University of Venice, I-30172 Venezia, Italy
- Doctoral School in Molecular Biomedicine, University of Trieste, I-34149 Trieste, Italy
| | - Giorgia Pastorin
- Pharmacy Department, National University of Singapore, Block S9, Level 15, 4 Science Drive 2, Singapore 117544, Singapore
| | - Gabriele Grassi
- Department of Life Sciences, Cattinara University Hospital, Trieste University, Strada di Fiume 447, I-34149 Trieste, Italy
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8
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Lu C, Jiang Y, Xu W, Bao X. Sestrin2: multifaceted functions, molecular basis, and its implications in liver diseases. Cell Death Dis 2023; 14:160. [PMID: 36841824 PMCID: PMC9968343 DOI: 10.1038/s41419-023-05669-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Revised: 02/08/2023] [Accepted: 02/09/2023] [Indexed: 02/26/2023]
Abstract
Sestrin2 (SESN2), a highly conserved stress-responsive protein, can be triggered by various noxious stimuli, such as hypoxia, DNA damage, oxidative stress, endoplasmic reticulum (ER) stress, and inflammation. Multiple transcription factors regulate SESN2 expression, including hypoxia-inducible factor 1 (HIF-1), p53, nuclear factor E2-related factor 2 (Nrf2), activating transcription factor 4 (ATF4), ATF6, etc. Upon induction, SESN2 generally leads to activation of adenosine monophosphate-activated protein kinase (AMPK) and inhibition of mechanistic target of rapamycin complex 1 (mTORC1). To maintain cellular homeostasis, SESN2 and its downstream molecules directly scavenge reactive oxygen species or indirectly influence the expression patterns of key genes associated with redox, macroautophagy, mitophagy, ER stress, apoptosis, protein synthesis, and inflammation. In liver diseases including acute liver injury, fatty liver diseases, hepatic fibrosis, and hepatocellular carcinoma (HCC), SESN2 is abnormally expressed and correlated with disease progression. In NAFLD, SESN2 helps with postponing disease progression through balancing glycolipid metabolism and macroautophagy (lipophagy), and rectifying oxidative damage and ER stress. During hepatic fibrosis, SESN2 represses HSCs activation and intrahepatic inflammation, hindering the occurrence and progress of fibrogenesis. However, the role of SESN2 in HCC is controversial due to its paradoxical pro-autophagic and anti-apoptotic effects. In conclusion, this review summarizes the biological functions of SESN2 in hypoxia, genotoxic stress, oxidative stress, ER stress, and inflammation, and specifically emphasizes the pathophysiological significance of SESN2 in liver diseases, aiming to providing a comprehensive understanding for SESN2 as a potential therapeutic target in liver diseases.
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Affiliation(s)
- Chunfeng Lu
- grid.260483.b0000 0000 9530 8833School of Pharmacy, Nantong University, 226001 Nantong, Jiangsu China
| | - Yiming Jiang
- grid.260483.b0000 0000 9530 8833School of Pharmacy, Nantong University, 226001 Nantong, Jiangsu China
| | - Wenxuan Xu
- School of Life Science and Technology, China Pharmaceutical University, 210009, Nanjing, Jiangsu, China.
| | - Xiaofeng Bao
- School of Pharmacy, Nantong University, 226001, Nantong, Jiangsu, China.
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Xu Y, Luan G, Li Z, Liu Z, Qin G, Chu Y. Tumour-derived exosomal lncRNA SNHG16 induces telocytes to promote metastasis of hepatocellular carcinoma via the miR-942-3p/MMP9 axis. Cell Oncol (Dordr) 2022; 46:251-264. [PMID: 36434360 DOI: 10.1007/s13402-022-00746-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/02/2022] [Indexed: 11/26/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) cell-derived exosomal LncRNA SNHG16 is highly expressed and associated with poor overall survival of patients. Telocytes (TCs), as novel interstitial cells, have been reported to promote HCC metastasis. Therefore, in our study, we investigated whether a molecular interaction occurred between exosomal LncSNHG16 and TCs in the tumor microenvironment. METHODS LncSNHG16 expression in HCC tissues and cell lines was measured, and bioinformatics analysis was performed. Exosomes were isolated and purified from HCC cells with LncSNHG16 overexpression/knockdown vectors and cocultured with TCs. Then, markers of the LncSNHG16/miR-942-3p/MMP9 axis were tested in TCs. Transwell assays and cell wound healing assays were designed to examine the invasion and migration of HCC cells after coincubation with TCs. RNA immunoprecipitation (RIP) assays and dual-luciferase gene reporter assays were performed to verify the binding effect of LncSNHG16, miR-942-3p, and MMP9 mRNA. In vivo, experimental animal models were established to confirm the effect of exosomal LncSNHG16-induced MMP9 expression on HCC metastasis. RESULTS Exosomal LncSNHG16 was phagocytized by TCs and downregulated miR-942-3p, which induced targeted MMP9 upregulation, and it had specific binding sites with miR-942-3p in TCs to facilitate the migration of HCC cells in vitro and in vivo. Exosomal LncSNHG16 was found to act as a competing endogenous RNA of the miR-942-3p/MMP9 axis in TCs. CONCLUSION Tumour-derived exosomal LncSNHG16 modulates MMP9 via competitively binding to miR-942-3p in TCs, thus promoting the metastasis of HCC.
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Affiliation(s)
- Ying Xu
- Shandong Cancer Hospital and Institute, Shandong Fist Medical University and Shandong Academy of Medical Science, No 440, Jiyan Road, Ji'nan, Shandong, China.
| | | | - Zhongchao Li
- Shandong Cancer Hospital and Institute, Shandong Fist Medical University and Shandong Academy of Medical Science, No 440, Jiyan Road, Ji'nan, Shandong, China
| | - Ziming Liu
- Shandong Fist Medical University and Shandong Academy of Medical Science, Ji'nan, Shandong, China
| | - Guangyang Qin
- Shandong Fist Medical University and Shandong Academy of Medical Science, Ji'nan, Shandong, China
| | - Yifu Chu
- Shandong Fist Medical University and Shandong Academy of Medical Science, Ji'nan, Shandong, China
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Tang Y, Zhang H, Chen L, Zhang T, Xu N, Huang Z. Identification of Hypoxia-Related Prognostic Signature and Competing Endogenous RNA Regulatory Axes in Hepatocellular Carcinoma. Int J Mol Sci 2022; 23:13590. [PMID: 36362375 PMCID: PMC9658439 DOI: 10.3390/ijms232113590] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 10/24/2022] [Accepted: 10/27/2022] [Indexed: 11/27/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is a common type of liver cancer and one of the highly lethal diseases worldwide. Hypoxia plays an important role in the development and prognosis of HCC. This study aimed to construct a new hypoxia-related prognosis signature and investigate its potential ceRNA axes in HCC. RNA profiles and hypoxia genes were downloaded, respectively, from the Cancer Genome Atlas hepatocellular carcinoma database and Gene Set Enrichment Analysis website. Cox regression analyses were performed to select the prognostic genes and construct the risk model. The ENCORI database was applied to build the lncRNA-miRNA-mRNA prognosis-related network. The TIMER and CellMiner databases were employed to analyze the association of gene expression in ceRNA with immune infiltration and drug sensitivity, respectively. Finally, the co-expression analysis was carried out to construct the potential lncRNA/miRNA/mRNA regulatory axes. We obtained a prognostic signature including eight hypoxia genes (ENO2, KDELR3, PFKP, SLC2A1, PGF, PPFIA4, SAP30, and TKTL1) and further established a hypoxia-related prognostic ceRNA network including 17 lncRNAs, six miRNAs, and seven mRNAs for hepatocellular carcinoma. Then, the analysis of immune infiltration and drug sensitivity showed that gene expression in the ceRNA network was significantly correlated with the infiltration abundance of multiple immune cells, the expression level of immune checkpoints, and drug sensitivity. Finally, we identified three ceRNA regulatory axes (SNHG1/miR-101-3p/PPFIA4, SNHG1/miR-101-3p/SAP30, and SNHG1/miR-101-3p/TKTL1) associated with the progression of HCC under hypoxia. Here, we constructed a prognosis gene signature and a ceRNA network related to hypoxia for hepatocellular carcinoma. Among the ceRNA network, six highly expressed lncRNAs (AC005540.1, AC012146.1, AC073529.1, AC090772.3, AC138150.2, AL390728.6) and one highly expressed mRNA (PPFIA4) were the potential biomarkers of hepatocellular carcinoma which we firstly reported. The three predicted hypoxia-related regulatory axes may play a vital role in the progression of hepatocellular carcinoma.
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Affiliation(s)
- Yulai Tang
- The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523710, China
- The First Clinical Medical College, Guangdong Medical University, Dongguan 523808, China
| | - Hua Zhang
- The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523710, China
- Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University, Key Laboratory of Computer-Aided Drug Design of Dongguan City, Key Laboratory for Research and Development of Natural Drugs of Guangdong Province, Guangdong Medical University, Dongguan 523808, China
| | - Lingli Chen
- The First Clinical Medical College, Guangdong Medical University, Dongguan 523808, China
| | - Taomin Zhang
- Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University, Key Laboratory of Computer-Aided Drug Design of Dongguan City, Key Laboratory for Research and Development of Natural Drugs of Guangdong Province, Guangdong Medical University, Dongguan 523808, China
| | - Na Xu
- Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University, Key Laboratory of Computer-Aided Drug Design of Dongguan City, Key Laboratory for Research and Development of Natural Drugs of Guangdong Province, Guangdong Medical University, Dongguan 523808, China
| | - Zunnan Huang
- The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523710, China
- Key Laboratory of Big Data Mining and Precision Drug Design of Guangdong Medical University, Key Laboratory of Computer-Aided Drug Design of Dongguan City, Key Laboratory for Research and Development of Natural Drugs of Guangdong Province, Guangdong Medical University, Dongguan 523808, China
- Marine Medical Research Institute of Guangdong Zhanjiang, Zhanjiang 524023, China
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11
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The Clinical Value of Long Noncoding RNA DDX11-AS1 as a Biomarker for the Diagnosis and Prognosis of Hepatocellular Carcinoma. JOURNAL OF ONCOLOGY 2022; 2022:5735462. [PMID: 36072974 PMCID: PMC9444391 DOI: 10.1155/2022/5735462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 07/23/2022] [Accepted: 07/26/2022] [Indexed: 11/17/2022]
Abstract
Hepatocellular carcinoma (HCC) is a high-mortality malignant tumor with genetic and phenotypic heterogeneity, making predicting clinical outcomes challenging. The purpose of this investigation was to examine the potential usefulness of lncRNA DDX11 antisense RNA 1 (DDX11-AS1) as a biomarker for diagnosis and prognosis in hepatocellular carcinoma (HCC). The TCGA-LIHC datasets were searched for patients’ clinical information and RNA-seq data, which were then collected. Relative expression levels of DDX11-AS1 in HCC tissues were determined by qRT-PCR. In order to test the sensitivity and specificity of the DDX11-AS1 receiver, receiver operating characteristic curves were utilized. The association of DDX11-AS1 expression with clinicopathological factors or prognosis was statistically analyzed. We found that the levels of DDX11-AS1 were higher in HCC specimens than in normal specimens. ROC analysis showed that DDX11-AS1 was a useful marker for discriminating HCC tissues from normal nontumor specimens. According to the results of clinical tests, a high level of DDX11-AS1 expressions was significantly related to the pathologic stage (
) and the histologic grade (
). Survival studies indicated that patients with higher DDX11-AS1 expression had a significantly poorer overall survival (
) and progression-free interval (
) than those with lower DDX11-AS1 expression. Multivariate survival analysis verified that DDX11-AS1 expression level was an independent predictor for HCC patients. Overall, DDX11-AS1 may serve as a tumor promotor during HCC progression, and its high level may be a potential marker for HCC patients.
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12
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Youssef SS, Elfiky A, Nabeel MM, Shousha HI, Elbaz T, Omran D, Marie MS, Elzahry MA, Abul-Fotouh A, Hashem A, Guda MF, Abdelaziz AO. Assessment of circulating levels of microRNA-326, microRNA-424, and microRNA-511 as biomarkers for hepatocellular carcinoma in Egyptians. World J Hepatol 2022; 14:1562-1575. [PMID: 36157872 PMCID: PMC9453463 DOI: 10.4254/wjh.v14.i8.1562] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Revised: 01/14/2022] [Accepted: 07/31/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is the fifth most common cancer. Differential expression of microRNAs (miRNAs)-326, miRNA-424, and miRNA-511 has been associated with the diagnosis and prognosis of HCC in different populations. However, limited information is available regarding their expression in Egyptian HCC patients.
AIM To assess the role of circulating miRNAs-326, miRNA-424, and miRNA-511 in Egyptian HCC patients.
METHODS This prospective observational study included 70 HCC patients and 25 healthy controls. The circulating levels of these three miRNAs were evaluated by real-time PCR. Receiver operating characteristic curve analysis was used to test the diagnostic accuracy of microRNA expression levels.
RESULTS All miRNAs were differentially expressed in HCC patients; miRNAs326 and miRNA-424 were upregulated, while miRNA-511 was downregulated. Both miRNA-326 and miRNA-424 showed sensitivity and specificity of 97%, 71.4%, and 52%, 60%, respectively, to differentiate HCC from controls. Moreover, miRNA-326 was associated with survival and could differentiate between Child grades (A vs B); miRNA-424 significantly differentiated early vs intermediate stages of HCC; while miRNA-511 was significantly correlated with response to modified Response Evaluation Criteria in Solid Tumors (mRECIST).
CONCLUSION We conclude that miRNA-326, miRNA-424, and miRNA-511 have diagnostic and prognostic roles in Egyptian patients with hepatitis C virus-related HCC and should be considered for better disease management.
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Affiliation(s)
- Samar Samir Youssef
- Department of Microbial Biotechnology, National Research Centre, Cairo 1211, Egypt
| | - Asmaa Elfiky
- Department of Environmental and Occupational Medicine, National Research Centre, Cairo 1211, Egypt
| | - Mohamed M Nabeel
- Department of Endemic Medicine and Hepatogastroenterology, Faculty of Medicine, Cairo University, Cairo 11562 Egypt
| | - Hend Ibrahim Shousha
- Department of Endemic Medicine and Hepatogastroenterology, Faculty of Medicine, Cairo University, Cairo 11562 Egypt
| | - Tamer Elbaz
- Department of Endemic Medicine and Hepatogastroenterology, Faculty of Medicine, Cairo University, Cairo 11562 Egypt
| | - Dalia Omran
- Department of Endemic Medicine, Faculty of Medicine, Cairo University, Cairo 1256, Egypt
| | - Mohammad Saeed Marie
- Department of Endemic Medicine and Hepatogastroenterology, Faculty of Medicine, Cairo University, Cairo 11562 Egypt
| | - Mohammad A Elzahry
- Department of Endemic Medicine, Faculty of Medicine, Cairo University, Cairo 1256, Egypt
| | - Amr Abul-Fotouh
- Department of Endemic Medicine, Faculty of Medicine, Cairo University, Cairo 1256, Egypt
| | - Ahmed Hashem
- Department of Endemic Medicine, Faculty of Medicine, Cairo University, Cairo 1256, Egypt
| | | | - Ashraf O Abdelaziz
- Department of Endemic Medicine and Hepatogastroenterology, Faculty of Medicine, Cairo University, Cairo 11562 Egypt
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13
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Sequence Requirements for miR-424-5p Regulating and Function in Cancers. Int J Mol Sci 2022; 23:ijms23074037. [PMID: 35409396 PMCID: PMC8999618 DOI: 10.3390/ijms23074037] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Revised: 04/02/2022] [Accepted: 04/05/2022] [Indexed: 12/13/2022] Open
Abstract
MiRNAs (microRNAs) are the most abundant family of small noncoding RNAs in mammalian cells. Increasing evidence shows that miRNAs are crucial regulators of individual development and cell homeostasis by controlling various biological processes. Therefore, miRNA dysfunction can lead to human diseases, especially in cancers with high morbidity and mortality worldwide. MiRNAs play different roles in these processes. In recent years, studies have found that miR-424-5p is closely related to the occurrence, development, prognosis and treatment of tumors. This review discusses how miR-424-5p plays a role in different kinds of cancers from different stages of tumors, including its roles in (i) promoting or inhibiting tumorigenesis, (ii) regulating tumor development in the tumor microenvironment and (iii) participating in cancer chemotherapy. This review provides a deep discussion of the latest findings on miR-424-5p and its importance in cancer, as well as a mechanistic analysis of the role of miR-424-5p in various tissues through target gene verification and pathway analysis.
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14
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Lv HC, Lv YY, Wang G, Zhang XH, Li SN, Yue XF, Lu W. Mechanism of miR-424-5p promoter methylation in promoting epithelial-mesenchymal transition of hepatocellular carcinoma cells. Kaohsiung J Med Sci 2022; 38:336-346. [PMID: 35049148 DOI: 10.1002/kjm2.12499] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Revised: 10/26/2021] [Accepted: 11/18/2021] [Indexed: 11/05/2022] Open
Abstract
The current study set out to clarify the role of miR-424-5p promoter methylation in epithelial mesenchymal transition (EMT) of hepatocellular carcinoma (HCC) cells. The findings of quantitative real-time-polymerase chain reaction and methylation-sensitive high-resolution melting assays elicited that miR-424-5p was poorly expressed in HCC tissues and cells while highly methylated. Meanwhile, upon demethylation, miR-424-5p expression levels were partly recovered in HCC cells. In addition, miR-424-5p upregulation reduced cell viability and elevated apoptosis of HCC cells, in parallel with increased N-cadherin and decreased E-cadherin levels. Dual-luciferase reporter assay further validated that miR-424-5p bound to the kinesin family member 2A (KIF2A), and miR-424-5p overexpression downregulated KIF2A. In addition, KIF2A overexpression reversed the miR-424-5p-driven changes in terms of cell viability, apoptosis and EMT-related protein levels. Furthermore, xenograft tumors were established via injection of Huh7 cells, followed by miR-424-5p overexpression in vivo, which inhabited KIF2A downregulation and attenuated tumor growth along with decreased Ki67 positive expression, diminished N-cadherin and elevated E-cadherin levels. Overall, our findings supported the conclusion that miR-424-5p promoter methylation reduced miR-424-5p expression and upregulated KIF2A, thereby promoting HCC EMT.
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Affiliation(s)
- Hong-Cheng Lv
- Department of Hepatobiliary Oncology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin, China
| | - Yan-Yan Lv
- Tianjin Second People's Hospital, Tianjin, China
| | - Gang Wang
- Tianjin Union Medical Center, Tianjin, China
| | - Xie-Hua Zhang
- Department of Hepatobiliary Oncology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin, China.,Department of infectious diseases, The First Affiliated Hospital of Baotou Medical College, Baotou, China
| | - Sheng-Nan Li
- Department of Hepatobiliary Oncology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin, China.,Tianjin Second People's Hospital, Tianjin, China
| | - Xiao-Fen Yue
- Department of Hepatobiliary Oncology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin, China.,Tianjin Second People's Hospital, Tianjin, China
| | - Wei Lu
- Department of Hepatobiliary Oncology, Liver Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin, China
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15
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Chang Q, Wu J, An Y, Liu H, Sun Y. Propofol suppresses proliferation, migration, invasion, and tumor growth of liver cancer cells via suppressing cancer susceptibility candidate 9/phosphatase and tensin homolog/AKT serine/threonine kinase/mechanistic target of rapamycin kinase axis. Hum Exp Toxicol 2022; 41:9603271211065972. [PMID: 35238236 DOI: 10.1177/09603271211065972] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Propofol is a commonly used drug for sedation and general anesthesia during cancer surgery. Previous studies indicate that propofol exerts anti-tumor effect in various cancers. The aim of this study was to investigate the underlying molecular mechanism of propofol in liver cancer. The effects of propofol on liver cancer cells were evaluated by cell viability assay, colony formation assay, and tumor xenograft model. Dysregulated lncRNAs of propofol-treated liver cancer cells were evaluated by transcriptome RNA sequencing. The underlying molecular mechanisms of lncRNA cancer susceptibility candidate 9 (CASC9) in propofol-induced anti-tumor effects were evaluated by western blot, quantitative real-time polymerase chain reaction (qRT-PCR), wound scratch healing assay, transwell cell migration and invasion assay, TUNEL staining, fluorescence in situ hybridization, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP). We found that propofol suppressed proliferation, migration, invasion, and tumor xenograft growth of liver cancer cells in a dose-dependent manner. Exosomes transfer from propofol-treated cells inhibited proliferation, migration, and invasion and promoted apoptosis of liver cancer cells. Transcriptional profiling of propofol-treated liver cancer cells identified CASC9 as significantly downregulated lncRNA in cells and exosomes. Enforced CASC9 expression partially rescued the inhibitory effects of propofol on liver cancer cells. Furthermore, CASC9 was found to interact directly with EZH2 and epigenetically regulated PTEN expression. Restoration of CASC9 partially abrogated the inhibition of propofol on Akt/mTOR signaling. Our results indicated that propofol exerted anti-tumor effects by downregulating CASC9, and subsequently suppressed Akt/mTOR signaling. Our findings provided a novel insight into propofol-induced anti-tumor effects in liver cancer.
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Affiliation(s)
- Qing Chang
- Department of anesthesiology, Heilongjiang Provincal Hospital(Harbin Institute of Technology, Heilongjiang Provincal Hospital), No. 82 Zhongshan Rd, Harbin 150036, China
| | - Jun Wu
- Department of anesthesiology, Heilongjiang Provincal Hospital(Harbin Institute of Technology, Heilongjiang Provincal Hospital), No. 82 Zhongshan Rd, Harbin 150036, China
| | - Yang An
- Department of anesthesiology, Heilongjiang Provincal Hospital(Harbin Institute of Technology, Heilongjiang Provincal Hospital), No. 82 Zhongshan Rd, Harbin 150036, China
| | - Haiyan Liu
- Department of anesthesiology, Heilongjiang Provincal Hospital(Harbin Institute of Technology, Heilongjiang Provincal Hospital), No. 82 Zhongshan Rd, Harbin 150036, China
| | - Yang Sun
- Department of anesthesiology, Heilongjiang Provincal Hospital(Harbin Institute of Technology, Heilongjiang Provincal Hospital), No. 82 Zhongshan Rd, Harbin 150036, China
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16
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Jiao Y, Liu Q, Zhao H, Hu X, Sun J, Liu X. Changes and Prognostic Value of lncRNA CASC9 in Patients with Advanced Colon Cancer after Chemotherapy. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2021; 2021:1858974. [PMID: 34589129 PMCID: PMC8476242 DOI: 10.1155/2021/1858974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Accepted: 08/29/2021] [Indexed: 11/18/2022]
Abstract
OBJECTIVE Colon cancer (CC) shows a gradual increasing incidence in recent years, and chemotherapy is a frequently adopted treatment for patients with middle or advanced colon cancer (ACC), but it lacks prognostic markers after CC. METHODS The changes of lncRNA CASC9 in 58 patients with CC were determined using a real-time quantitative PCR (qRT-PCR) assay before and after chemotherapy, and the correlation of serum lncRNA CASC9 with efficacy of FOLFOX4 regimen (oxaliplatin + calcium folinate + fluorouracil) was analyzed. The patients were followed up to understand the association of lncRNA CASC9 with overall survival (OS) and progression-free survival (PFS). RESULTS Patients with CC showed notably higher lncRNA CASC9 expression than controls, and lncRNA CASC9 presented an association with the clinical stage of the patients. In addition, lncRNA CASC9 demonstrated a clinical value in predicting efficacy on patients and acted as one independent prognostic factor for PFS in patients with ACC. CONCLUSIONS With increased expression of serum lncRNA CASC9, patients with ACC suffered an unfavorable chemotherapy effect. In addition, serum lncRNA CASC9 is a promising sensitive indicator for prediction of ACC and is related to the clinical efficacy and prognosis of patients.
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Affiliation(s)
- Yingwei Jiao
- Department of Proctology, Shaanxi Nuclear Industry 215 Hospital, Xianyang, Shaanxi 712000, China
| | - Qiang Liu
- Department of Proctology, Shaanxi Nuclear Industry 215 Hospital, Xianyang, Shaanxi 712000, China
| | - Hongbo Zhao
- Department of Proctology, Shaanxi Nuclear Industry 215 Hospital, Xianyang, Shaanxi 712000, China
| | - Xianzhen Hu
- Four Departments of General Surgery, Shaanxi Nuclear Industry 215 Hospital, Xianyang, Shaanxi 712000, China
| | - Jinlong Sun
- Department of Proctology, Shaanxi Nuclear Industry 215 Hospital, Xianyang, Shaanxi 712000, China
| | - Xiaohong Liu
- Department of Traditional Chinese Medicine, Baoji Maternal and Child Health Care Hospital, Baoji, Shaanxi 721000, China
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