|
1
|
Gu Y, Feng Z, Xu X, Jin L. Identification of a novel immune-related gene signature by single-cell and bulk sequencing for the prediction of the immune landscape and prognosis of breast cancer. Cancer Cell Int 2024; 24:393. [PMID: 39627792 PMCID: PMC11613745 DOI: 10.1186/s12935-024-03589-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 11/26/2024] [Indexed: 12/08/2024] Open
Abstract
BACKGROUND As a common cause of cancer-related deaths in women, BRCA (breast cancer) shows complexity and requires precise biomarkers and treatment methods. This study delves into the molecular makeup of BRCA, focusing on immune profiles, molecular subtypes, gene expression and single-cell analysis. METHODS XCell was used to assess immune infiltration based on TCGA (the Cancer Genome Atlas) data and the clustering analysis was made. Differentially expressed genes were examined in distinct clusters, and the WGCNA (weighted correlation network analysis) was made to establish co-expression networks. The prognostic models were developed by Cox and LASSO-Cox regression. The clustering analysis, GSEA (Gene set enrichment analysis), GSVA (gene set variation analysis) and communication analysis of the single-cell dataset GSE161529 were performed to investigate the functional relevance. Real-time polymerase chain reaction (RT-PCR) was employed for evaluating gene expression. RESULTS The results revealed significant differences in immune cell infiltration between two clusters (C1 and C2). C2 had poorer survival outcomes, which was associated with higher expression of immune checkpoints PD1 and PD-L1. The gene modules identified via WGCNA were correlated with the immune-based subtypes. Then, a prognostic model comprising seven genes (ACSL1, ABCB5, XG, ADH4, OPN4, NPR3, NLGN1) was used to divide patients into high- and low-risk subgroups. The high-risk group had worse prognosis and higher scores of TIDE (Tumor Immune Dysfunction and Exclusion). The single-cell analysis depicted the immune landscape. Macrophages and endothelial cells exhibited higher AUCell scores. In cellular communication analysis, notably significant ligand-receptor interactions of HLA-DRA-> CD4 and TNFSF13B-> HLA-DPB1 were observed. The proportion of endothelial cells was correlated with risk scores. Finally, RT-PCR results illustrated the expression of seven genes in BRCA specimens. CONCLUSION The integrative analysis provides new insights into molecular complexities of BRCA. Immune profiles and gene signatures hold potential for improving stratification of BRCA patients and guiding the development of personalized immunotherapy strategies.
Collapse
Affiliation(s)
- Yanlin Gu
- Department of Thyroid and Breast Surgery, The Second Affiliated Hospital of Soochow University, Jiangsu, China
| | - Zhengyang Feng
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Jiangsu, China
| | - Xiaoyan Xu
- Department of Operating Room, Traditional Chinese Medicine Hospital of Kunshan, Jiangsu, China
| | - Liyan Jin
- Department of Thyroid and Breast Surgery, The Second Affiliated Hospital of Soochow University, Jiangsu, China.
| |
Collapse
|
|
2
|
Arima J, Yoshino H, Fukumoto W, Kawahara I, Saito S, Li G, Fukuda I, Iizasa S, Mitsuke A, Sakaguchi T, Inoguchi S, Matsushita R, Nakagawa M, Tatarano S, Yamada Y, Enokida H. LncRNA BCYRN1 as a Potential Therapeutic Target and Diagnostic Marker in Serum Exosomes in Bladder Cancer. Int J Mol Sci 2024; 25:5955. [PMID: 38892143 PMCID: PMC11172611 DOI: 10.3390/ijms25115955] [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: 03/29/2024] [Revised: 05/24/2024] [Accepted: 05/27/2024] [Indexed: 06/21/2024] Open
Abstract
Bladder cancer (BC) is a common genitourinary malignancy that exhibits silent morbidity and high mortality rates because of a lack of diagnostic markers and limited effective treatments. Here, we evaluated the role of the lncRNA brain cytoplasmic RNA 1 (BCYRN1) in BC. We performed loss-of-function assays to examine the effects of BCYRN1 downregulation in T24 and BOY BC cells. We found that BCYRN1 downregulation significantly inhibited the proliferation, migration, invasion, and three-dimensional spheroid formation ability and induced apoptosis in BC cells. Additionally, gene set enrichment analysis (GSEA) using RNA sequences from tumor fractions showed that BCYRN1 downregulation decreased the expression of mRNAs associated with the cell cycle. These findings were supported by observations of G2/M arrest in flow cytometry assays. Finally, we examined the expression of serum exosomal BCYRN1 as a biomarker. Clinically, BCYRN1 expression in serum exosomes from patients with BC (n = 31) was significantly higher than that in healthy donors (n = 19; mean difference: 4.1-fold higher, p < 0.01). Moreover, in patients who had undergone complete resection of BC, serum exosomal BCYRN1 levels were significantly decreased (n = 8). Thus, serum exosomal BCYRN1 may be a promising diagnostic marker and therapeutic target in patients with BC.
Collapse
Affiliation(s)
| | - Hirofumi Yoshino
- Department of Urology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
3
|
Han X, Leng C, Zhao S, Wang S, Chen S, Wang S, Zhang M, Li X, Lu Y, Wang B, Qi W. Development and verification of a manganese metabolism- and immune-related genes signature for prediction of prognosis and immune landscape in gastric cancer. Front Immunol 2024; 15:1377472. [PMID: 38807601 PMCID: PMC11131102 DOI: 10.3389/fimmu.2024.1377472] [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: 01/27/2024] [Accepted: 04/29/2024] [Indexed: 05/30/2024] Open
Abstract
Background Gastric cancer (GC) poses a global health challenge due to its widespread prevalence and unfavorable prognosis. Although immunotherapy has shown promise in clinical settings, its efficacy remains limited to a minority of GC patients. Manganese, recognized for its role in the body's anti-tumor immune response, has the potential to enhance the effectiveness of tumor treatment when combined with immune checkpoint inhibitors. Methods Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases was utilized to obtain transcriptome information and clinical data for GC. Unsupervised clustering was employed to stratify samples into distinct subtypes. Manganese metabolism- and immune-related genes (MIRGs) were identified in GC by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis. We conducted gene set variation analysis, and assessed the immune landscape, drug sensitivity, immunotherapy efficacy, and somatic mutations. The underlying role of NPR3 in GC was further analyzed in the single-cell RNA sequencing data and cellular experiments. Results GC patients were classified into four subtypes characterized by significantly different prognoses and tumor microenvironments. Thirteen genes were identified and established as MIRGs, demonstrating exceptional predictive effectiveness in GC patients. Distinct enrichment patterns of molecular functions and pathways were observed among various risk subgroups. Immune infiltration analysis revealed a significantly greater abundance of macrophages and monocytes in the high-risk group. Drug sensitivity analysis identified effective drugs for patients, while patients in the low-risk group could potentially benefit from immunotherapy. NPR3 expression was significantly downregulated in GC tissues. Single-cell RNA sequencing analysis indicated that the expression of NPR3 was distributed in endothelial cells. Cellular experiments demonstrated that NPR3 facilitated the proliferation of GC cells. Conclusion This is the first study to utilize manganese metabolism- and immune-related genes to identify the prognostic MIRGs for GC. The MIRGs not only reliably predicted the clinical outcome of GC patients but also hold the potential to guide future immunotherapy interventions for these patients.
Collapse
Affiliation(s)
- Xiaoxi Han
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Chuanyu Leng
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shufen Zhao
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shasha Wang
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shuming Chen
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shibo Wang
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Mengqi Zhang
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Xiangxue Li
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yangyang Lu
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Bing Wang
- Biomedical Centre, Qingdao University, Qingdao, China
| | - Weiwei Qi
- Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, China
| |
Collapse
|
|
4
|
Doghish AS, Zaki MB, Eldeib MG, Radwan AF, Moussa R, Abdel-Wahab MM, Kizilaslan EZ, Alhamshry NAA, Ashour AE, Elimam H. The potential relevance of long non-coding RNAs in colorectal cancer pathogenesis and treatment: A review focus on signaling pathways. Pathol Res Pract 2024; 253:155044. [PMID: 38141573 DOI: 10.1016/j.prp.2023.155044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 12/17/2023] [Accepted: 12/18/2023] [Indexed: 12/25/2023]
Abstract
Colorectal cancer (CRC) is one of the most frequent cancers in incidence and mortality. Despite advances in cancer biology, molecular genetics, and targeted treatments, CRC prognosis and survival have not kept pace. This is usually due to advanced staging and metastases at diagnosis. Thus, great importance has been placed upon understanding the molecular pathophysiology behind the development of CRC, which has highlighted the significance of non-coding RNA's role and associated intracellular signaling pathways in the pathogenesis of the disease. According to recent studies, long non-coding RNAs (lncRNA), a subtype of ncRNAs whose length exceeds 200 nucleotides, have been found to have regulatory functions on multiple levels. Their actions at the transcription, post-transcriptional, translational levels, and epigenetic regulation have made them prime modulators of gene expression. Due to their role in cellular cancer hallmarks, their dysregulation has been linked to several illnesses, including cancer. Furthermore, their clinical relevance has expanded due to their possible detection in blood which has cemented them as potential future biomarkers and thus, potential targets for new therapy. This review will highlight the importance of lncRNAs and related signaling pathways in the development of CRC and their subsequent clinical applications.
Collapse
Affiliation(s)
- Ahmed S Doghish
- Department of Biochemistry, Faculty of Pharmacy, Badr University in Cairo (BUC), Badr City, Cairo 11829, Egypt; Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt.
| | - Mohamed Bakr Zaki
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt
| | - Mahmoud Gomaa Eldeib
- Biochemistry and Molecular Biology Department, Faculty of Pharmacy (Boys), Al-Azhar University, Nasr City 11231, Cairo, Egypt; Department of Biochemistry, Faculty of Pharmacy, Sinai University - Kantara Branch, 41636 Ismailia, Egypt
| | - Abdullah F Radwan
- Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Cairo 11829, Egypt
| | - Rewan Moussa
- Faculty of Medicine, Helwan University, Cairo, Egypt
| | - Maie M Abdel-Wahab
- Department of Biochemistry, Faculty of Pharmacy, Sinai University - Kantara Branch, 41636 Ismailia, Egypt
| | | | - Nora A A Alhamshry
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt
| | - Abdelkader E Ashour
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, King Salman International University, Ras Sudr, South Sinai, Egypt
| | - Hanan Elimam
- Department of Biochemistry, Faculty of Pharmacy, University of Sadat City, Sadat City 32897, Egypt.
| |
Collapse
|
|
5
|
Dou Q, Ba F, Hu S, Xu GY, Wei J, Jiang GQ. LncRNA NONRATT014888.2 contributes to cancer-induced bone pain through downregulation of natriuretic peptide receptor 3 in rats. Biochem Biophys Res Commun 2023; 683:149114. [PMID: 37857164 DOI: 10.1016/j.bbrc.2023.10.046] [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: 08/05/2023] [Revised: 09/30/2023] [Accepted: 10/12/2023] [Indexed: 10/21/2023]
Abstract
Long noncoding RNA (lncRNA) is implicated in both cancer development and pain process. However, the role of lncRNA in the development of cancer-induced bone pain (CIBP) is unclear. LncRNA NONRATT014888.2 is highly expressed in tibia related dorsal root ganglions (DRGs) in CIBP rats which function is unknown. CIBP was induced by injection of Walker 256 mammary gland tumor cells into the tibia canal of female SD rats. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) of rats were measured. Down-regulation of NONRATT014888.2 by siRNA in CIBP rats markedly attenuated hind-paw mechanical pain hypersensitivity. LncRNA-predicted target mRNAs analysis and mRNA sequencing results cued Socs3, Npr3 were related with NONRATT014888.2. Intrathecal injection of NONRATT014888.2-siR206 upregulated Npr3 both in mRNA and protein level. Npr3 was co-expressed in NONRATT014888.2-positive DRGs neurons and mainly located in cytoplasm, but not in Glial fibrillary acidic protein (GFAP)-positive cells. Intrathecal injection of ADV-Npr3 upregulated Npr3 expression and enhanced the PWT of CIBP rats. Our results suggest that upregulated lncRNA NONRATT014888.2 contributed to hyperalgesia in CIBP rats, and the mechanism may through downregulation of Npr3.
Collapse
Affiliation(s)
- Qianshu Dou
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, 1055 San-Xiang Road, Suzhou, 215004, Jiangsu, PR China
| | - Futing Ba
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, 1055 San-Xiang Road, Suzhou, 215004, Jiangsu, PR China
| | - Shufen Hu
- Laboratory for Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou, 215123, PR China
| | - Guang-Yin Xu
- Laboratory for Translational Pain Medicine, Institute of Neuroscience, Soochow University, Suzhou, 215123, PR China
| | - Jinrong Wei
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, 1055 San-Xiang Road, Suzhou, 215004, Jiangsu, PR China.
| | - Guo-Qin Jiang
- Department of General Surgery, The Second Affiliated Hospital of Soochow University, 1055 San-Xiang Road, Suzhou, 215004, Jiangsu, PR China.
| |
Collapse
|
|
6
|
Li P, Zhong R, Yu J, Wang Y, Wang C, Geng W, Bao S, Wang S, Zhang G, Zhu X, Ji M, Guan H. DCLRE1A Contributes to DNA Damage Repair and Apoptosis in Age-Related Cataracts by Regulating the lncRNA/miRNA/mRNA Axis. Curr Eye Res 2023; 48:992-1005. [PMID: 37503815 DOI: 10.1080/02713683.2023.2241159] [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: 03/10/2023] [Accepted: 07/23/2023] [Indexed: 07/29/2023]
Abstract
PURPOSE Age-related cataract (ARC) is associated with the deregulation of transcription and defects in DNA repair in lens epithelial cells (LECs). DCLRE1A acted in DNA interstrand cross-links pathway to improve DNA replication and transcription. The aim of this study was to examined the further regulatory effect on DCLRE1A in the lncRNA-miRNA-mRNA network using a cell model of DCLRE1A overexpression (OE-DCLRE1A) in LECs. METHODS The expression level of DCLRE1A in ARC tissues and SRA01/04 cells after H2O2 treatment was measured as protein and mRNA by qRT-PCR and Western Blot(WB). CCK8, and TUNEL assays detected the change in cell viability and apoptosis, respectively. Furthermore, Immunofluorescence assays detect the expression of DNA damaged and repair marker proteins after OE-DCLRE1A. The global expression profiles of lncRNAs, miRNAs, and mRNAs were determined using high-throughput sequencing. KEGG and GO enrichment analysis disclose the possible function of differentially expressed (DE) lncRNA, miRNA, and mRNA. RESULTS The protein and mRNA of DCLRE1A were decreased in the anterior capsule of ARC and SRA01/04 cells treated by H2O2. OE-DCLRE1A improved damaged-DNA repair and enhanced cell viability against apoptosis after H2O2 treatment. Furthermore, we demonstrated the DE-molecules between the OE-DCLRE1A and control groups including 595 DE-lncRNAs, 221 DE-miRNAs, and 4718 DE-mRNAs. Next, bioinformatics analysis not only found that the DE-mRNAs are mainly involved in DNA repair-related signaling pathways after OE-DCLRE1A, but also screened two lncRNA-miRNA-mRNA networks focusing on DNA damage activated by OE-DCLRE1A, which involved 2 lncRNAs, 2 miRNAs, and 53 mRNAs. CONCLUSION We revealed that DCLRE1A activated the lncRNA/miRNA/DNA-repair network to take part in DNA repair processes, which not only represents a new regulatory mechanism employed by DCLRE1A but also uncovers the screening lncRNA may hold potential therapeutic values in ARC formation. However, these conclusions will need to be confirmed by future studies in vitro and in vivo models.
Collapse
Affiliation(s)
- Pengfei Li
- Eye Institute, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China
| | - Renhao Zhong
- Eye Institute, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China
| | - Jianfeng Yu
- Eye Institute, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China
| | - Ying Wang
- Department of Ophthalmology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China
| | - Congyu Wang
- Eye Institute, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China
| | - Wenjing Geng
- Eye Institute, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China
| | - Sijie Bao
- Eye Institute, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China
| | - Siwen Wang
- Eye Institute, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China
| | - Guowei Zhang
- Eye Institute, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China
| | - Xi Zhu
- Eye Institute, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China
| | - Min Ji
- Eye Institute, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China
| | - Huaijin Guan
- Eye Institute, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, Jiangsu, China
| |
Collapse
|
|
7
|
Lv W, He X, Wang Y, Zhao C, Dong M, Wu Y, Zhang Q. A novel immune score model predicting the prognosis and immunotherapy response of breast cancer. Sci Rep 2023; 13:6403. [PMID: 37076508 PMCID: PMC10115816 DOI: 10.1038/s41598-023-31153-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Accepted: 03/07/2023] [Indexed: 04/21/2023] Open
Abstract
Breast cancer (BC) is one of the most common malignancies. However, the existing pathological grading system cannot accurately and effectively predict the survival rate and immune checkpoint treatment response of BC patients. In this study, based on The Cancer Genome Atlas (TCGA) database, a total of 7 immune-related genes (IRGs) were screened out to construct a prognostic model. Subsequently, the clinical prognosis, pathological characteristics, cancer-immunity cycle, tumour immune dysfunction and exclusion (TIDE) score, and immune checkpoint inhibitor (ICI) response were compared between the high- and low-risk groups. In addition, we determined the potential regulatory effect of NPR3 on BC cell proliferation, migration, and apoptosis. The model consisting of 7 IRGs was an independent prognostic factor. Patients with lower risk scores exhibited longer survival times. Moreover, the expression of NPR3 was increased but the expression of PD-1, PD-L1, and CTLA-4 was decreased in the high-risk group compared to the low-risk group. In addition, compared with si-NC, si-NPR3 suppressed proliferation and migration but promoted apoptosis in both MDA-MB-231 and MCF-7 cells. This study presents a model for predicting survival outcomes and provides a strategy to guide effective personalized immunotherapy in BC patients.
Collapse
Affiliation(s)
- Wenchang Lv
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
| | - Xiao He
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
| | - Yichen Wang
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
| | - Chongru Zhao
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China
| | - Menglu Dong
- Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China.
| | - Yiping Wu
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China.
| | - Qi Zhang
- Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China.
| |
Collapse
|
|
8
|
Han XY, Li X, Zhao RY, Ma HZ, Yu M, Niu XD, Jin HJ, Wang YF, Liu DM, Cai H. Comprehensive analysis of prognostic value and immunotherapy prospect of brain cytoplasmic RNA1 in hepatocellular carcinoma. World J Gastrointest Oncol 2023; 15:644-664. [PMID: 37123057 PMCID: PMC10134208 DOI: 10.4251/wjgo.v15.i4.644] [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: 11/24/2022] [Revised: 02/18/2023] [Accepted: 03/16/2023] [Indexed: 04/12/2023] Open
Abstract
BACKGROUND The expression of brain cytoplasmic RNA1 (BCYRN1) is linked to the clinicopathology and prognosis of several types of cancers, among which hepatocellular carcinoma (HCC) is one of the most frequent types of cancer worldwide.
AIM To explore the prognostic value and immunotherapeutic potential of BCYRN1 in HCC by bioinformatics and meta-analysis.
METHODS Information was obtained from the Cancer Genome Atlas database. First, the correlation between BCYRN1 expression and prognosis and clinicopathologic characteristics of HCC patients was explored. Univariate and multivariate regression analyses were employed to examine the relationship between BCYRN1 and HCC prognosis. Secondly, potential functions and pathways were explored by means of enrichment analysis of differentially-expressed genes. The relationships between BCYRN1 expression and tumor microenvironment, immune cell infiltration, immune checkpoint, drug sensitivity and immunotherapy effect were also investigated. Finally, three major databases were searched and used to conduct a meta-analysis on the relationship between BCYRN1 expression and patient prognosis.
RESULTS BCYRN1 expression was significantly higher in HCC compared to normal tissues and was linked to a poor prognosis and clinicopathological characteristics. Enrichment analysis showed that BCYRN1 regulates the extracellular matrix and transmission of signaling molecules, participates in the metabolism of nutrients, such as proteins, and participates in tumor-related pathways. BCYRN1 expression was linked to the tumor microenvironment, immune cell infiltration, drug sensitivity and the efficacy of immunotherapy. Furthermore, the meta-analysis in this study showed that BCYRN1 overexpression was related to a worse outcome in HCC patients.
CONCLUSION Overexpression of BCYRN1 relates to poor prognosis and may be a potential prognostic factor and immunotherapeutic target in HCC.
Collapse
Affiliation(s)
- Xiao-Yong Han
- Gansu General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
- Graduate School, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Xiong Li
- Gansu General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
- Graduate School, Ningxia Medical University, Yinchuan 750004, Ningxia Hui Autonomous Region, China
| | - Rang-Yin Zhao
- Gansu General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
- The First Clinical Medical College, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
| | - Hai-Zhong Ma
- Gansu General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
- The First Clinical College of Medicine, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Miao Yu
- Gansu General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Xiang-Dong Niu
- Gansu General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Hao-Jie Jin
- The First Clinical College of Medicine, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - Yong-Feng Wang
- Gansu General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
- The First Clinical College of Medicine, Lanzhou University, Lanzhou 730000, Gansu Province, China
| | - De-Ming Liu
- Gansu General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| | - Hui Cai
- Gansu General Surgery Clinical Medical Center, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
- Key Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
- Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou 730000, Gansu Province, China
- NHC Key Laboratory of Diagnosis and Therapy of Gastrointestinal Tumor, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
| |
Collapse
|
|
9
|
Zang J, Sun J, Xiu W, Liu X, Chai Y, Zhou Y. Low Expression of AGPAT5 Is Associated With Clinical Stage and Poor
Prognosis in Colorectal Cancer and Contributes to Tumour
Progression. Clin Med Insights Oncol 2022; 16:11795549221137399. [PMCID: PMC9716453 DOI: 10.1177/11795549221137399] [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: 05/16/2022] [Accepted: 10/20/2022] [Indexed: 12/05/2022] Open
Abstract
Background: Colorectal cancer (CRC) has a high prevalence and poor prognosis. This study
aimed to identify biomarkers related to the clinical stage (I-IV) of
CRC. Methods: The LinkedOmics database was used as the discovery cohort, and two Gene
Expression Omnibus (GEO) databases (GSE41258 and GSE422848) served as
validation cohorts. The trend test of genes related to clinical stage (I-IV)
of CRC patients was identified by the Jonckheere-Terpstra test. The
cBioPortal database, Gene Expression Profiling Interactive Analysis (GEPIA)
and PrognoScan databases were used to explore the expression change and
prognostic value of clinical stage-related genes in CRC patients. CRC cells
overexpressed AGPAT5 were constructed and used for cell counting kit-8
(CCK-8), flow cytometric, and wound healing assays in vitro. Results: We identified four clinical stage-related genes, GSR, AGPAT5, CRLF1, and
NPR3, in CRC. The CNA frequencies of GSR, CRLF1, AGPAT5, and NPR3 occurred
in 11%, 2.4%, 13%, and 3% of patients, respectively. The expression of GSR
and AGPAT5 tended to decrease with CRC stage (I-IV) progression, and the
expression of CRLF1 and NPR3 tended to increase with CRC stage (I-IV)
progression. Compared with the normal group, AGPAT5 expression was markedly
decreased in stage IV CRC. Higher GSR and AGPAT5 expression levels were
associated with better overall survival (OS) and disease-free survival (DFS)
in CRC patients. Lower CRLF1 and NPR3 expression levels were associated with
better OS and DFS in CRC. GSR, CRLF1, AGPAT5, and NPR3 expression were
related to CRC progression, microsatellite instability, and tumour purity in
CRC. Furthermore, AGPAT5 was downregulated in CRC cell lines, and
overexpression of AGPAT5 inhibited cell proliferation and migration and
promoted cell apoptosis in CRC cells. Conclusion: Low AGPAT5 expression may serve as a poor prognostic factor and clinical
stage biomarker in CRC. In addition, AGPAT5 acts as a tumour suppressor in
CRC progression.
Collapse
Affiliation(s)
- Jia Zang
- Department of Colorectal Surgery,
Shanghai Changzheng Hospital, Shanghai, P.R. China
| | - Juanjuan Sun
- Department of Colorectal Surgery,
Shanghai Changzheng Hospital, Shanghai, P.R. China
| | - WenChao Xiu
- The Second Ward of Anorectal
Department, Qilu Hospital of Shandong University (Qingdao), China
| | - Xiaoshuang Liu
- Department of General Surgery, Shuguang
Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P.R.
China
| | - Yunsheng Chai
- Department of Colorectal Surgery,
Shanghai Changzheng Hospital, Shanghai, P.R. China,Yunsheng Chai, Department of Colorectal
Surgery, Shanghai Changzheng Hospital, No. 415, FengYang Road, Shanghai 200003,
P.R. China.
| | - Yanyan Zhou
- Department of Colorectal Surgery,
Shanghai Changzheng Hospital, Shanghai, P.R. China
| |
Collapse
|
|
10
|
Tseng YC, Shu CW, Chang HM, Lin YH, Tseng YH, Hsu HS, Goan YG, Tseng CJ. Next Generation Sequencing for Potential Regulated Genes and Micro-RNAs of Early Growth Response-1 in the Esophageal Squamous Cell Carcinoma. Protein J 2022; 41:563-571. [PMID: 36207572 DOI: 10.1007/s10930-022-10079-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/21/2022] [Indexed: 11/25/2022]
Abstract
Esophageal cancer has a poor prognosis due to its aggressiveness and low survival rate. In Ease Asia, esophageal squamous cell carcinoma (ESCC) outnumbers esophageal adenocarcinoma (EAC). The ESCC patients still have high mortality despite modern surgical resection and neoadjuvant treatment. Determining patient and outcome prognostic factors is critical in ESCC treatment. In esophageal cancer, early growth response-1 (Egr-1) is a tumor suppressor gene, but the mechanism and associated genes are unknown. The study utilizes RNA interference method, the platform of Next Generation Sequencing (NGS) and bioinformatics analysis to investigate the influences after the Egr-1 gene slicing on the ESCC cells. The heat maps of differentially expressed mRNA and microRNAs were analyzed using the algorithm, Burrows-Wheller Aligner. The study showed that the expression of 51 mRNA and 26 microRNAs have significant changes in ESCC cells after Egr-1 knockdown. The KEGG enrichment analysis linked Egr-1-regulated genes and microRNAs. Egr-1 interactions with these genes and microRNAs may be important in tumor progression. In conclusions, this study provided the transcriptome patterns and relating pathway analysis for Egr-1 knockdown in ESCC cells. The mRNA and microRNAs altered by Egr-1 gene silencing might provide key information in the treatment of ESCC.
Collapse
Affiliation(s)
- Yen-Chiang Tseng
- Division of Thoracic Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chih-Wen Shu
- Institute of BioPharmaceutical Sciences, National Sun Yat-Sen University, No. 70, Lianhai Rd., Gushan Dist, Kaohsiung, 80424, Taiwan. .,Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, 80708, Taiwan.
| | - Hui-Min Chang
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Rd., Zuoying Dist, Kaohsiung, 81362, Taiwan
| | - Yi-Hsuan Lin
- Department of Family Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Yen-Han Tseng
- Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Han-Shui Hsu
- Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan.,School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.,Institute of Emergency and Critical Care Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Yih-Gang Goan
- Division of Thoracic Surgery, Department of Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.,School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ching-Jiunn Tseng
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan. .,Department of Medical Education and Research, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Rd., Zuoying Dist, Kaohsiung, 81362, Taiwan.
| |
Collapse
|
|
11
|
Fu J, Sun H, Xu F, Chen R, Wang X, Ding Q, Xia T. RUNX regulated immune-associated genes predicts prognosis in breast cancer. Front Genet 2022; 13:960489. [PMID: 36092942 PMCID: PMC9459239 DOI: 10.3389/fgene.2022.960489] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2022] [Accepted: 07/25/2022] [Indexed: 12/03/2022] Open
Abstract
Background: Breast cancer is the most common malignant tumor in women. RUNX family has been involved in the regulation of different carcinogenic processes and signaling pathways with cancer, which is closely related to immunity and prognosis of various tumors, and also plays an important role in the development and prognosis of breast cancer. Methods: We discovered the expression of RUNX family through GEPIA Dataset and then evaluated the relationship between RUNX family and immune-related genes and the prognosis of breast cancer through analyzing TCGA database. A prognostic model was established and verified via cox proportional hazards regression model using R packages. We evaluated the accuracy of the prognostic model by Kaplan-Meier curves and receiver operating characteristic (ROC) curves. Additionally, we obtained the relationship between the RUNX family and immune infiltration by TIMER database. Finally, the dual luciferase reporter assay was used to verify the regulation of RUNX3 on potential target genes ULBP2 and TRDV1, and the effects of ULBP2 and TRDV1 on the growth of breast cancer cells were explored by CCK-8, colony formation and wound healing assays. Results: We screened out RUNX family-regulated immune-related genes associated with the prognosis of breast cancer. These predictors included PSME2, ULBP2, IL-18, TSLP, NPR3, TRDV1. Then a prognosis-related risk score model was built using the independent risk factors to provide a clinically appropriate method predicting the overall survival (OS) probability of the patients with breast cancer. In addition, a further research was made on the functions of high risk immune gene ULBP2 and low risk immune gene TRDV1 which regulated by RUNX3, the results showed that down-regulation of ULBP2 suppressed breast cancer cell proliferation and TRDV1 had the opposite functions. The prognostic model we constructed could promote the development of prognostic, and was associated with lower immune infiltration. Conclusion: The expression of RUNX family was closely related to the prognosis of breast cancer. At the same time, RUNX family could modulate the functions of immune-related genes, and affect the development and prognosis of breast cancer. These immune-related genes regulated by RUNX family could be promising prognostic biomarkers and therapeutic targets in breast cancer.
Collapse
Affiliation(s)
| | | | | | | | | | - Qiang Ding
- *Correspondence: Tiansong Xia, ; Qiang Ding,
| | | |
Collapse
|
|
12
|
Clinicopathological Significance and Prognostic Values of Long Noncoding RNA BCYRN1 in Cancer Patients: A Meta-Analysis and Bioinformatics Analysis. JOURNAL OF ONCOLOGY 2022; 2022:8903265. [PMID: 35874631 PMCID: PMC9303157 DOI: 10.1155/2022/8903265] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 06/14/2022] [Indexed: 12/24/2022]
Abstract
Background Although combination therapies have substantially improved the clinical outcomes of cancer patients, the prognosis and early diagnosis remain unsatisfactory. As a result, it is critical to look for novel indicators linked to cancer. Despite a number of recent studies indicating that the lncRNA brain cytoplasmic RNA1(BCYRN1) may be a potential predictive biomarker in cancer patients, BCYRN1's prognostic value is still being debated. Methods We utilized PubMed, Embase, Web of Science, and the Cochrane Library to search for studies related to BCYRN1 until October 2021. Valid data were extracted after determining the articles according to the inclusion and exclusion criteria, and forest plots were made using Stata software. We used hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals to evaluate the relationship between abnormal BCYRN1 expression and patient prognosis and clinicopathological characteristics. Results Meta-analysis revealed that increased BCYRN1 expression was associated with both overall tumor survival (OS; HR = 1.84, 95% CI 1.51–2.25, p < 0.0001) and disease-free survival (DFS; HR = 1.65, 95% CI 1.20–2.26, p=0.002). Furthermore, a strong association was discovered between increased BCYRN1 expression and tumor invasion depth (OR = 2.11, 95% CI 1.49–2.99, p=0.000), clinical stage (OR = 2.52, 95% CI 1.18–5.37, p=0.017), and distant tumor metastasis (OR = 4.19, 95% CI 1.45–12.05, p=0.008). Conclusions We found that high BCYRN1 expression was associated with poor survival prognosis and aggressive clinicopathological characteristics in various cancers, indicating that it is a potential prognostic indicator as well as a therapeutic target. Further research is needed on pan-cancer cohorts to determine the clinical relevance of BCYRN1 in distinct cancer types.
Collapse
|
|
13
|
Nomiri S, Hoshyar R, Chamani E, Rezaei Z, Salmani F, Larki P, Tavakoli T, Gholipour F, Tabrizi NJ, Derakhshani A, Santarpia M, Franchina T, Brunetti O, Silvestris N, Safarpour H. Prediction and validation of GUCA2B as the hub-gene in colorectal cancer based on co-expression network analysis: In-silico and in-vivo study. Biomed Pharmacother 2022; 147:112691. [PMID: 35151227 DOI: 10.1016/j.biopha.2022.112691] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Revised: 01/25/2022] [Accepted: 02/02/2022] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Several serious attempts to treat colorectal cancer have been made in recent decades. However, no effective treatment has yet been discovered due to the complexities of its etiology. METHODS we used Weighted Gene Co-expression Network Analysis (WGCNA) to identify key modules, hub-genes, and mRNA-miRNA regulatory networks associated with CRC. Next, enrichment analysis of modules has been performed using Cluepedia. Next, quantitative real-time PCR (RT-qPCR) was used to validate the expression of selected hub-genes in CRC tissues. RESULTS Based on the WGCNA results, the brown module had a significant positive correlation (r = 0.98, p-value=9e-07) with CRC. Using the survival and DEGs analyses, 22 genes were identified as hub-genes. Next, three candidate hub-genes were selected for RT-qPCR validation, and 22 pairs of cancerous and non-cancerous tissues were collected from CRC patients referred to the Gastroenterology and Liver Clinic. The RT-qPCR results revealed that the expression of GUCA2B was significantly reduced in CRC tissues, which is consistent with the results of differential expression analysis. Finally, top miRNAs correlated with GUCA2B were identified, and ROC analyses revealed that GUCA2B has a high diagnostic performance for CRC. CONCLUSIONS The current study discovered key modules and GUCA2B as a hub-gene associated with CRC, providing references to understand the pathogenesis and be considered a novel candidate to CRC target therapy.
Collapse
Affiliation(s)
- Samira Nomiri
- Department of Clinical Biochemistry, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Reyhane Hoshyar
- Department of Clinical Biochemistry, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Elham Chamani
- Department of Clinical Biochemistry, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Zohreh Rezaei
- Department of Biology, Faculty of Sciences, University of Sistan and Balouchestan, Zahedan, Iran
| | - Fatemeh Salmani
- Department of Epidemiology and Biostatistics, Social Determinants of Health Research Center, Faculty of Health, Birjand University of Medical Sciences, Birjand, Iran
| | - Pegah Larki
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Tahmine Tavakoli
- Cardiovascular Research Center, Birjand University of Medical Sciences, Birjand, Iran
| | - Faranak Gholipour
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Neda Jalili Tabrizi
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Afshin Derakhshani
- Laboratory of Experimental Pharmacology, IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy
| | - Mariacarmela Santarpia
- Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, Messina, Italy
| | - Tindara Franchina
- Medical Oncology Unit, Department of Human Pathology "G. Barresi", University of Messina, Messina, Italy
| | - Oronzo Brunetti
- Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II" of Bari, Bari, Italy
| | - Nicola Silvestris
- Medical Oncology Unit, IRCCS Istituto Tumori "Giovanni Paolo II" of Bari, Bari, Italy; Department of Biomedical Sciences and Human Oncology (DIMO), University of Bari, Bari, Italy.
| | - Hossein Safarpour
- Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran.
| |
Collapse
|
|
14
|
KRAS-related long noncoding RNAs in human cancers. Cancer Gene Ther 2022; 29:418-427. [PMID: 34489556 PMCID: PMC9113938 DOI: 10.1038/s41417-021-00381-x] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 06/29/2021] [Accepted: 08/11/2021] [Indexed: 02/08/2023]
Abstract
KRAS is one of the most widely prevalent proto-oncogenes in human cancers. The constitutively active KRAS oncoprotein contributes to both tumor onset and cancer development by promoting cell proliferation and anchorage-independent growth in a MAPK pathway-dependent manner. The expression of microRNAs (miRNAs) and the KRAS oncogene are known to be dysregulated in various cancers, while long noncoding RNAs (lncRNAs) can act as regulators of the miRNAs targeting KRAS oncogene in different cancers and have gradually become a focus of research in recent years. In this review article, we summarize recent advances in the research on lncRNAs that have sponging effects on KRAS-targeting miRNAs as crucial mediators of KRAS expression in different cell types and organs. A deeper understanding of lncRNA function in KRAS-driven cancers is of major fundamental importance and will provide a valuable clinical tool for the diagnosis, prognosis, and eventual treatment of cancers.
Collapse
|
|
15
|
Morotti A, Cetani F, Passoni G, Borsari S, Pardi E, Guarnieri V, Verdelli C, Tavanti GS, Valenti L, Bianco C, Ferrero S, Corbetta S, Vaira V. The Long Non-Coding BC200 Is a Novel Circulating Biomarker of Parathyroid Carcinoma. Front Endocrinol (Lausanne) 2022; 13:869006. [PMID: 35586620 PMCID: PMC9108332 DOI: 10.3389/fendo.2022.869006] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 04/04/2022] [Indexed: 01/10/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) are an important class of epigenetic regulators involved in both physiological processes and cancer development. Preliminary evidence suggested that lncRNAs could act as accurate prognostic and diagnostic biomarkers. Parathyroid cancer is a rare endocrine neoplasia, whose management represents a clinical challenge due to the lack of accurate molecular biomarkers. Our previous findings showed that human parathyroid tumors are characterized by a different lncRNAs signature, suggesting heterogeneity through the different histotypes. Particularly, we found that the lncRNA BC200/BCYRN1 could represent a candidate biomarker for parathyroid carcinomas (PCas). Here we aimed to extend our preliminary data evaluating whether BC200 could be an accurate non-invasive biomarker of PCas to support the clinical management of patients affected by parathyroid tumors at diagnosis, prognosis and follow-up. To provide a non-invasive point-of-care for parathyroid carcinoma diagnosis and follow-up, we analyzed BC200 expression in patients' serum through digital PCR. Our results show that BC200 counts are higher in serum from patients harboring PCa (n=4) compared to patients with parathyroid adenoma (PAd; n=27). Further, in PAd patients circulating BC200 levels are positively correlated with serum total calcium. Then, we found that BC200 is overexpressed in metastatic PCas (n=4) compared to non-metastatic ones (n=9). Finally, the lncRNA expression in PCa patients' serum drops are reduced after parathyroidectomy, suggesting its possible use in the post-operative setting for patients follow-up. Overall, these findings extend the knowledge on BC200 in parathyroid tumors, supporting its role as a useful biomarker for management of PCa.
Collapse
Affiliation(s)
- Annamaria Morotti
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
- Division of Pathology, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Milan, Italy
| | | | - Giulia Passoni
- Division of Pathology, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Milan, Italy
| | - Simona Borsari
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Elena Pardi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Vito Guarnieri
- Division of Medical Genetics, Fondazione IRCCS Casa Sollievo della Sofferenza, Foggia, Italy
| | - Chiara Verdelli
- Laboratory of Experimental Endocrinology, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
| | - Giulia Stefania Tavanti
- Endocrinology and Diabetology Service, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
| | - Luca Valenti
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
- Precision Medicine – Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Cristiana Bianco
- Precision Medicine – Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Stefano Ferrero
- Division of Pathology, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Milan, Italy
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
| | - Sabrina Corbetta
- Endocrinology and Diabetology Service, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
- *Correspondence: Valentina Vaira, ; Sabrina Corbetta,
| | - Valentina Vaira
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
- Division of Pathology, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Milan, Italy
- *Correspondence: Valentina Vaira, ; Sabrina Corbetta,
| |
Collapse
|
|
16
|
Ton TVT, Kovi RC, Peddada TN, Chhabria RM, Shockley KR, Flagler ND, Gerrish KE, Herbert RA, Behl M, Hoenerhoff MJ, Sills RC, Pandiri AR. Cobalt-induced oxidative stress contributes to alveolar/bronchiolar carcinogenesis in B6C3F1/N mice. Arch Toxicol 2021; 95:3171-3190. [PMID: 34468815 DOI: 10.1007/s00204-021-03146-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2020] [Accepted: 08/19/2021] [Indexed: 12/19/2022]
Abstract
Rodent alveolar/bronchiolar carcinomas (ABC) that arise either spontaneously or due to chemical exposure are similar to a subtype of lung adenocarcinomas in humans. B6C3F1/N mice and F344/NTac rats exposed to cobalt metal dust (CMD) by inhalation developed ABCs in a dose dependent manner. In CMD-exposed mice, the incidence of Kras mutations in ABCs was 67% with 80% of those being G to T transversions on codon 12 suggesting a role of oxidative stress in the pathogenesis. In vitro studies, such as DMPO (5,5-dimethyl-1-pyrroline N-oxide) immune-spin trapping assay, and dihydroethidium (DHE) fluorescence assay on A549 and BEAS-2B cells demonstrated increased oxidative stress due to cobalt exposure. In addition, significantly increased 8-oxo-dG adducts were demonstrated by immunohistochemistry in lungs from mice exposed to CMD for 90 days. Furthermore, transcriptomic analysis on ABCs arising spontaneously or due to chronic CMD-exposure demonstrated significant alterations in canonical pathways related to MAPK signaling (IL-8, ErbB, Integrin, and PAK pathway) and oxidative stress (PI3K/AKT and Melatonin pathway) in ABCs from CMD-exposed mice. Oxidative stress can stimulate PI3K/AKT and MAPK signaling pathways. Nox4 was significantly upregulated only in CMD-exposed ABCs and NOX4 activation of PI3K/AKT can lead to increased ROS levels in human cancer cells. The gene encoding Ereg was markedly up-regulated in CMD-exposed mice. Oncogenic KRAS mutations have been shown to induce EREG overexpression. Collectively, all these data suggest that oxidative stress plays a significant role in CMD-induced pulmonary carcinogenesis in rodents and these findings may also be relevant in the context of human lung cancers.
Collapse
Affiliation(s)
- Thai-Vu T Ton
- Comparative and Molecular Pathogenesis Branch, DNTP, NIEHS, 111 T.W. Alexander Drive, Research Triangle Park, NC, 27709, USA
| | - Ramesh C Kovi
- Comparative and Molecular Pathogenesis Branch, DNTP, NIEHS, 111 T.W. Alexander Drive, Research Triangle Park, NC, 27709, USA.,Experimental Pathology Laboratories Inc., Research Triangle Park, NC, 27709, USA.,Drug Safety Research and Development, Pfizer Inc., Cambridge, MA, USA
| | - Teja N Peddada
- Comparative and Molecular Pathogenesis Branch, DNTP, NIEHS, 111 T.W. Alexander Drive, Research Triangle Park, NC, 27709, USA.,National Institute of Mental Health, Bethesda, MD, 20892, USA
| | - Raveena M Chhabria
- Comparative and Molecular Pathogenesis Branch, DNTP, NIEHS, 111 T.W. Alexander Drive, Research Triangle Park, NC, 27709, USA.,Wake Forest University School of Medicine, Winston-Salem, NC, 27157, USA
| | - Keith R Shockley
- Biostatistics and Computational Biology Branch, NIEHS, Research Triangle Park, NC, 27709, USA
| | - Norris D Flagler
- Comparative and Molecular Pathogenesis Branch, DNTP, NIEHS, 111 T.W. Alexander Drive, Research Triangle Park, NC, 27709, USA
| | - Kevin E Gerrish
- Molecular Genomics Core Laboratory, NIEHS, Research Triangle Park, NC, 27709, USA
| | - Ronald A Herbert
- Comparative and Molecular Pathogenesis Branch, DNTP, NIEHS, 111 T.W. Alexander Drive, Research Triangle Park, NC, 27709, USA
| | - Mamta Behl
- Toxicology Branch, DNTP, NIEHS, Research Triangle Park, NC, 27709, USA
| | - Mark J Hoenerhoff
- Comparative and Molecular Pathogenesis Branch, DNTP, NIEHS, 111 T.W. Alexander Drive, Research Triangle Park, NC, 27709, USA.,In Vivo Animal Core, Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA
| | - Robert C Sills
- Comparative and Molecular Pathogenesis Branch, DNTP, NIEHS, 111 T.W. Alexander Drive, Research Triangle Park, NC, 27709, USA
| | - Arun R Pandiri
- Comparative and Molecular Pathogenesis Branch, DNTP, NIEHS, 111 T.W. Alexander Drive, Research Triangle Park, NC, 27709, USA.
| |
Collapse
|
|
17
|
Research updates on the clinical implication of long noncoding RNA in digestive system cancers and chemoresistance. 3 Biotech 2021; 11:423. [PMID: 34603923 DOI: 10.1007/s13205-021-02971-w] [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: 03/20/2021] [Accepted: 08/19/2021] [Indexed: 10/20/2022] Open
Abstract
Long noncoding RNAs (lncRNAs) are implicated in various biological processes, such as cell proliferation, differentiation, apoptosis, migration, and invasion. They are also key players in various biological pathways. LncRNA was considered as 'translational noise' before 1980s. It has been reported that lncRNAs are aberrantly expressed in different cancers, either as oncogene or tumor suppressor gene. Therefore, more and more lncRNAs are recognized as potential diagnostic biomarkers and/or therapeutic targets. As competitive endogenous RNA, lncRNAs can interact with microRNA to alter the expression of target genes, which may have extensive clinical implications in cancers, including diagnosis, treatment, prognosis, and chemoresistance. This review comprehensively summarizes the functions and clinical relevance of lncRNAs in digestive system cancers, especially as a potential tool to overcome chemoresistance.
Collapse
|
|
18
|
Li S, Guo R, Peng Z, Quan B, Hu Y, Wang Y, Wang Y. NPR3, transcriptionally regulated by POU2F1, inhibits osteosarcoma cell growth through blocking the PI3K/AKT pathway. Cell Signal 2021; 86:110074. [PMID: 34229087 DOI: 10.1016/j.cellsig.2021.110074] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2021] [Revised: 06/17/2021] [Accepted: 07/01/2021] [Indexed: 12/31/2022]
Abstract
Natriuretic peptide receptor 3 (NPR3), mediates natriuretic peptides degradation, was reported to act as a tumor suppressor or promoter in some types of cancer. Previous studies showed that NPR3 was significantly decreased in osteosarcoma (OS) samples. However, the function and potential regulatory mechanism of NPR3 in OS development are unknown. By analyzing the protein expression of NPR3 in OS cell lines (n = 5) and human osteoblast cell line hFOB 1.19, we found that NPR3 expression was also significantly decreased in OS cells. The loss/gain-of-function analysis indicated that NPR3 overexpression observably decreased OS cell viability, arrested cell cycle, and induced apoptosis. However, NPR3 knockdown further enhanced the malignant phenotype of OS cells. Furthermore, NPR3 downregulation activated the PI3K/AKT pathway in OS cells, and the effects of NPR3 silencing on cell proliferation were reversed by the blockade of PI3K/AKT pathway. Of note, dual-luciferase reported assay and site-directed mutagenesis assay indicated that transcription factor POU domain class 2 transcription factor 1 (POU2F1) was proved to suppress NPR3 promoter activity by mainly binding to the -900 to -800 bp region of NPR3 promoter. Moreover, NPR3 overexpression inversed the promotion effect of POU2F1 on cell proliferation. In vivo experiments confirmed that NPR3 overexpression suppressed the growth of xenograft tumors. Taken together, the present study demonstrates that NPR3 may serve as a novel tumor suppressive factor through blocking the PI3K/AKT pathway and transcriptionally regulated by POU2F1.
Collapse
Affiliation(s)
- Shuo Li
- The Fifth Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China; The Second Department of Orthopedics, The First Hospital of Qiqihar, Qiqihar, Heilongjiang Province, People's Republic of China
| | - Ruirong Guo
- The Fifth Department of Cardiology, The First Hospital of Qiqihar, Qiqihar, Heilongjiang Province, People's Republic of China
| | - Zhibin Peng
- The Fifth Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China
| | - Bingxuan Quan
- The Fifth Department of Orthopedics, Affiliated Hospital of Chifeng University, Chifeng, People's Republic of China
| | - Yuhang Hu
- The Fourth Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China
| | - Yiwen Wang
- The Fifth Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China
| | - Yansong Wang
- The Fifth Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, People's Republic of China.
| |
Collapse
|
|
19
|
Li H, Liu J, Lai Y, Huang S, Zheng L, Fan N. LINC01559 promotes colorectal cancer via sponging miR-1343-3p to modulate PARP1/PTEN/AKT pathway. Pathol Res Pract 2021; 224:153521. [PMID: 34329839 DOI: 10.1016/j.prp.2021.153521] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Revised: 06/03/2021] [Accepted: 06/06/2021] [Indexed: 10/21/2022]
Abstract
BACKGROUND Colorectal cancer (CRC) is considered as one of the commonest tumors and is the major reason of cancer-related deaths around the world. Plentiful evidences have validated that long non-coding RNAs (lncRNAs) play a significant part in various cancers, including CRC. LINC01559 is implicated in the development of various cancers. However, the detailed function of LINC01559 in CRC has not been illustrated. METHODS LINC01559 expression was examined via RT-qPCR, and a series of functional experiments were conducted to explore the role of LINC01559 in CRC progression. Mechanism experiments were carried out to examine the underlying mechanism of LINC01559. RESULTS LINC01559 expression was increased in CRC cells and tissues, and LINC01559 depletion restrained the biological behaviors of CRC cells. Also, LINC01559 sponged miR-1343-3p in CRC, and PARP1 was the target of miR-1343-3p. Besides, miR-1343-3p overexpression or PARP1 down-regulation affected the biological behaviors of CRC cells. In addition, up-regulation of PARP1 or adding SC79 (AKT pathway activator) could remedy the repressive effects of LINC01559 silencing on CRC cell biological behaviors. CONCLUSIONS LINC01559 promotes CRC through sponging miR-1343-3p to modulate PARP1/PTEN/AKT pathway, which may be conducive to offering a new idea for CRC therapeutic treatment.
Collapse
Affiliation(s)
- Hui Li
- Fujian Cancer Hospital & Institute, No 420 Fuma Road, Fuzhou, Fujian, 350014, China
| | - Jie Liu
- Fujian Cancer Hospital & Institute, No 420 Fuma Road, Fuzhou, Fujian, 350014, China
| | - Yiqin Lai
- Fujian Cancer Hospital & Institute, No 420 Fuma Road, Fuzhou, Fujian, 350014, China
| | - Sha Huang
- Fujian Cancer Hospital & Institute, No 420 Fuma Road, Fuzhou, Fujian, 350014, China
| | - Liang Zheng
- Fujian Cancer Hospital & Institute, No 420 Fuma Road, Fuzhou, Fujian, 350014, China
| | - Nanfen Fan
- Fujian Cancer Hospital & Institute, No 420 Fuma Road, Fuzhou, Fujian, 350014, China.
| |
Collapse
|
|
20
|
Huang PS, Chang CC, Wang CS, Lin KH. Functional roles of non-coding RNAs regulated by thyroid hormones in liver cancer. Biomed J 2021; 44:272-284. [PMID: 33077406 PMCID: PMC8358202 DOI: 10.1016/j.bj.2020.08.009] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 08/19/2020] [Accepted: 08/24/2020] [Indexed: 02/06/2023] Open
Abstract
Recent reports have shown the important role of the non-coding part of human genome RNA (ncRNA) in cancer formation and progression. Among several kinds of ncRNAs, microRNAs (miRNA) play a pivotal role in cancer biology. Accumulating researches have been focused on the importance of non-coding genes in various diseases. In addition to miRNAs, long non-coding RNAs (lncRNAs) have also been extensively documented. Recently, the study of human liver cancer has gradually shifted to these non-coding RNAs that were originally considered "junk". Notably, dysregulated ncRNAs maybe influence on cell proliferation, angiogenesis, anti-apoptosis, and metastasis. Thyroid hormones play critical roles in human development and abnormalities in thyroid hormone levels are associated with various diseases, such as liver cancer. Thyroid hormone receptors (TR) act as ligand-activated nuclear transcription factors to affect multiple functions through the gene-level regulation in the cells and several studies have revealed that thyroid hormone associated with ncRNAs expression. TR actions are complex and tissue- and time-specific, aberrant expression of the various TR isoforms have different effects and are associated with different types of tumor or stages of development. In this review, we discuss various aspects of the research on the thyroid hormones modulated ncRNAs to affect the functions of human liver cells.
Collapse
Affiliation(s)
- Po-Shuan Huang
- Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Cheng-Chih Chang
- Department of General Surgery, Chang Gung Memorial Hospital at Chia yi, Chia yi, Taiwan
| | - Chia-Siu Wang
- Department of General Surgery, Chang Gung Memorial Hospital at Chia yi, Chia yi, Taiwan
| | - Kwang-Huei Lin
- Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan; Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
| |
Collapse
|
|
21
|
Xu X, Lu Y, Wu Y, Wang M, Wang X, Wang H, Chen B, Li Y. A signature of seven immune-related genes predicts overall survival in male gastric cancer patients. Cancer Cell Int 2021; 21:117. [PMID: 33602220 PMCID: PMC7891008 DOI: 10.1186/s12935-021-01823-0] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2020] [Revised: 01/06/2021] [Accepted: 02/09/2021] [Indexed: 12/24/2022] Open
Abstract
Background Gastric cancer (GC) has a high mortality rate and is one of the most fatal malignant tumours. Male sex has been proven as an independent risk factor for GC. This study aimed to identify immune-related genes (IRGs) associated with the prognosis of male GC. Methods RNA sequencing and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed IRGs between male GC and normal tissues were identified by integrated bioinformatics analysis. Univariate and multivariate Cox regression analyses were applied to screen survival-associated IRGs. Then, GC patients were separated into high- and low-risk groups based on the median risk score. Furthermore, a nomogram was constructed based on the TCGA dataset. The prognostic value of the risk signature model was evaluated by Kaplan-Meier curve, receiver operating characteristic (ROC), Harrell’s concordance index and calibration curves. In addition, the gene expression dataset from the Gene Expression Omnibus (GEO) was also downloaded for external validation. The relative proportions of 22 types of infiltrating immune cells in each male GC sample were evaluated using CIBERSORT. Results
A total of 276 differentially expressed IRGs were screened, including 189 up-regulated and 87 down-regulated genes. Subsequently, a seven-IRGs signature (LCN12, CCL21, RNASE2, CGB5, NRG4, AGTR1 and NPR3) was identified to be significantly associated with the overall survival (OS) of male GC patients. Survival analysis indicated that patients in the high-risk group exhibited a poor clinical outcome. The results of multivariate analysis revealed that the risk score was an independent prognostic factor. The established nomogram could be used to evaluate the prognosis of individual male GC patients. Further analysis showed that the prognostic model had excellent predictive performance in both TCGA and validated cohorts. Besides, the results of tumour-infiltrating immune cell analysis indicated that the seven-IRGs signature could reflect the status of the tumour immune microenvironment. Conclusions Our study developed a novel seven-IRGs risk signature for individualized survival prediction of male GC patients.
Collapse
Affiliation(s)
- Xin Xu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Avenue, Hefei, 230022, Anhui, China.,Anhui Medical University, Hefei, 230022, China
| | - Yida Lu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Avenue, Hefei, 230022, Anhui, China.,Anhui Medical University, Hefei, 230022, China
| | - Youliang Wu
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Avenue, Hefei, 230022, Anhui, China.,Anhui Medical University, Hefei, 230022, China
| | - Mingliang Wang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Avenue, Hefei, 230022, Anhui, China.,Anhui Medical University, Hefei, 230022, China
| | - Xiaodong Wang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Avenue, Hefei, 230022, Anhui, China.,Anhui Medical University, Hefei, 230022, China
| | - Huizhen Wang
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Avenue, Hefei, 230022, Anhui, China
| | - Bo Chen
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Avenue, Hefei, 230022, Anhui, China
| | - Yongxiang Li
- Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, 218 JiXi Avenue, Hefei, 230022, Anhui, China.
| |
Collapse
|
|
22
|
Ghafouri-Fard S, Dashti S, Hussen BM, Farsi M, Taheri M. BCYRN1: An oncogenic lncRNA in diverse cancers. Pathol Res Pract 2021; 220:153385. [PMID: 33647864 DOI: 10.1016/j.prp.2021.153385] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 02/10/2021] [Accepted: 02/13/2021] [Indexed: 12/14/2022]
Abstract
Brain cytoplasmic 200 (BC200) or alternatively named as brain cytoplasmic RNA 1 (BCYRN1) is a long non-coding RNA (lncRNA) primarily identified in the neurons. In addition to its participation in the pathogenesis of neurodegenerative disorders, it partake in the carcinogenesis process. Numerous in vitro studies have reported elevation of expression of BCYRN1 in cancer cell lines. Short hairpin-RNA-mediated silencing of BCYRN1 has attenuated growth of tumors in the animal models. Independent studies in esophageal squamous cell cancer, gastric cancer, colorectal cancer, hepatocellular carcinoma and non-small cell lung cancer have demonstrated association between elevated BCYRN1 levels and poor survival of patients. Taken together, BCYRN1 is an appropriate candidate for targeted therapies in the field of cancer.
Collapse
Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Sepideh Dashti
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Bashdar Mahmud Hussen
- Pharmacognosy Department, College of Pharmacy, Hawler Medical University, Erbil, Iraq
| | - Molood Farsi
- Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Mohammad Taheri
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
| |
Collapse
|
|
23
|
Abstract
In this review, Yeganeh et al. summarize different human diseases that have been linked to defects in the Pol III transcription apparatus or to Pol III products imbalance and discuss the possible underlying mechanisms. RNA polymerase (Pol) III is responsible for transcription of different noncoding genes in eukaryotic cells, whose RNA products have well-defined functions in translation and other biological processes for some, and functions that remain to be defined for others. For all of them, however, new functions are being described. For example, Pol III products have been reported to regulate certain proteins such as protein kinase R (PKR) by direct association, to constitute the source of very short RNAs with regulatory roles in gene expression, or to control microRNA levels by sequestration. Consistent with these many functions, deregulation of Pol III transcribed genes is associated with a large variety of human disorders. Here we review different human diseases that have been linked to defects in the Pol III transcription apparatus or to Pol III products imbalance and discuss the possible underlying mechanisms.
Collapse
Affiliation(s)
- Meghdad Yeganeh
- Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland
| | - Nouria Hernandez
- Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, 1015 Lausanne, Switzerland
| |
Collapse
|
|
24
|
BCYRN1 is correlated with progression and prognosis in gastric cancer. Biosci Rep 2020; 39:220767. [PMID: 31652309 PMCID: PMC6859112 DOI: 10.1042/bsr20190505] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Revised: 09/04/2019] [Accepted: 10/03/2019] [Indexed: 12/24/2022] Open
Abstract
Long non-coding RNA brain cytoplasmic RNA 1 (BCYRN1) has been found to play an important role in tumorigenesis of a variety of tumors including gastric cancer (GC). However, the prognostic significance and molecular mechanism of BCYRN1 was still unknown in GC. In the present study, we found BCYRN1 expression was dramatically elevated in GC tissues and cell lines, and positively associated with tumor depth, lymph node metastasis and clinical stage in patients with GC. Moreover, univariate and multivariate Cox regression analyses demonstrated that high BCYRN1 expression was independent prognostic factor for overall survival in GC patients. In lncRNA-microRNA interactome database, we found that there were putative binding sites between BCYRN1 and miR-204-5p. Furthermore, we confirmed that down-regulation of BCYRN1 inhibited GC cell proliferation, migration and invasion through directly up-regulated miR-204-5p expression. In conclusion, BCYRN1 acts as a promising prognostic predictor in GC patients and regulated GC cell proliferation, cell cycle, migration and invasion through targeting miR-204-5p.
Collapse
|
|
25
|
Yang L, Zhang Y, Bao J, Feng JF. Long non-coding RNA BCYRN1 exerts an oncogenic role in colorectal cancer by regulating the miR-204-3p/KRAS axis. Cancer Cell Int 2020; 20:453. [PMID: 32944001 PMCID: PMC7491190 DOI: 10.1186/s12935-020-01543-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2020] [Accepted: 09/05/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND It has been well documented that long non-coding RNAs (lncRNAs) regulate numerous characteristics of cancer, including proliferation, migration, metastasis, apoptosis, and even metabolism. LncRNA BCYRN1 (BCYRN1) is a newly identified brain cytoplasmic lncRNA with 200 nucleotides that was discovered to be highly expressed in tumour tissues, including those of hepatocellular carcinoma, gastric cancer and lung cancer. However, the roles of BCYRN1 in colorectal cancer (CRC) remain obscure. This study was designed to reveal the role of BCYRN1 in the occurrence and progression of CRC. METHODS RT-PCR was used to detect the expression level of BCYRN1 in tumour tissues and CRC cell lines. BCYRN1 was knocked down in CRC cells, and cell proliferation changes were evaluated by cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), and Ki-67 and proliferating cell nuclear antigen (PCNA) expression assays. Cell migration and invasion changes were evaluated by wound healing, Transwell and invasion-related protein expression assays. Flow cytometry analysis was used to assess whether BCYRN1 regulates the apoptosis of CRC cells. The dual luciferase reporter gene detects the competitive binding of BCYRN1 to miR-204-3p. In vivo experiments were performed to evaluate the effect of BCYRN1 on tumour development. TargetScan analysis and dual luciferase reporter gene assays were applied to detect the target gene of miR-204-3p. Rescue experiments verified that BCYRN1 affects CRC by regulating the effect of miR-204-3p on KRAS. RESULTS We found that compared with normal tissues and human intestinal epithelial cells (HIECs), CRC tumour tissues and cell lines had significantly increased BCYRN1 levels. We further determined that knockdown of BCYRN1 inhibited the proliferation, migration, and invasion and promoted the apoptosis of CRC cells. In addition, bioinformatics analysis and dual luciferase reporter assay showed that BCYRN1 served as a competitive endogenous RNA (ceRNA) to regulate the development of CRC through competitively binding to miR-204-3p. Further studies proved that overexpression of miR-204-3p reversed the effects of BCYRN1 on CRC. Next, TargetScan analysis and dual luciferase reporter assay indicated that KRAS is a target gene of miR-204-3p and is negatively regulated by miR-204-3p. A series of rescue experiments showed that BCYRN1 affected the occurrence and development of CRC by regulating the effects of miR-204-3p on KRAS. In addition, tumorigenesis experiments in a CRC mouse model confirmed that BCYRN1 downregulation effectively inhibited tumour growth. CONCLUSIONS Our findings suggest that BCYRN1 plays a carcinogenic role in CRC by regulating the miR-204-3p/KRAS axis.
Collapse
Affiliation(s)
- Liu Yang
- Department of Colorectal Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China
| | - Yinan Zhang
- Department of Colorectal Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Nanjing, China
| | - Jun Bao
- Department of Chemotherapy, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, No. 42 Baiziting, Nanjing, China
| | - Ji-Feng Feng
- Department of Chemotherapy, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, No. 42 Baiziting, Nanjing, China
| |
Collapse
|
|
26
|
Zhao R, Cao X, Jin S, Li R, Zhong Q, Jiang M, Han J, Guo C, Zong H. LncRNA BC200 Promotes Esophageal Squamous Cell Cancer Migration and Invasion and Can Regulate ATF4 Expression. Front Oncol 2020; 10:1392. [PMID: 32974142 PMCID: PMC7468420 DOI: 10.3389/fonc.2020.01392] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Accepted: 07/02/2020] [Indexed: 12/24/2022] Open
Abstract
Background: The main reason for esophageal squamous cell carcinoma (ESCC) treatment failure is metastasis. Little is known about the mechanisms involved in the metastasis of ESCC, and there is a lack of effective therapeutic targets. In our previous study, we found that patients with high levels of BC200 tended to have poor prognoses. Methods: First, we applied qRT-PCR to detect the expression level of BC200 in normal esophageal squamous epithelial cells and ESCC cells with different degrees of differentiation ability. Then, we changed BC200 expression by transfecting constructed lentiviruses that included BC200 shRNA (LV-BC200-shRNA, KD), negative control (CON053, NC), or BC200 gene (LV-BC200, BC200) to create BC200-deficient cell models in KYSE410 and KYSE70 cells and BC200 overexpression cell models in EC9706 cells and verified the transfection effect by qRT-PCR. Then, we examined cell migration by wound healing assay, invasion by Transwell assay, and proliferation by MTT assay and examined the metastasis ability in a xenograft mouse model. Gene expression profiling was performed to screen a panel of mRNAs following inhibition of BC200 expression. We then used ingenuity pathway analysis (IPA) to analyze the functions of the changed molecules and their interactions. The results from the microarray were validated by qRT-PCR and Western blotting. Results: In this study, we found that the expression of BC200 in poorly differentiated cell lines was significantly higher than that in well-differentiated cell lines. BC200 can significantly promote the migration and invasion but not the proliferation ability of ESCC cells in vitro and BC200 shRNA can significantly suppress tumor metastasis in vivo. Our genome-wide expression profile chip showed 406 differentially expressed genes, with 91 upregulated genes and 315 downregulated genes. The upstream regulator analysis showed that ATF4 was predicted to be strongly inhibited and 21 genes were consistently inhibited by this gene. Our qRT-PCR and Western blotting data also identified the reduced expression of ATF4 and some selected downstream genes, such as SNAIL2, GADD45A, and PSAT1, as a consequence of downregulating BC200 expression in ESCC. Conclusion: Our data showed that BC200 promoted the metastasis of ESCC cells and could regulate the expression of ATF4 and its downstream genes.
Collapse
Affiliation(s)
- Ruihua Zhao
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xinguang Cao
- Department of Digestive Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Shuiling Jin
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Rui Li
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Qian Zhong
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Miao Jiang
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jinming Han
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Changqing Guo
- Department of Digestive Disease, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Hong Zong
- Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| |
Collapse
|
|
27
|
Moon CI, Tompkins W, Wang Y, Godec A, Zhang X, Pipkorn P, Miller CA, Dehner C, Dahiya S, Hirbe AC. Unmasking Intra-tumoral Heterogeneity and Clonal Evolution in NF1-MPNST. Genes (Basel) 2020; 11:genes11050499. [PMID: 32369930 PMCID: PMC7291009 DOI: 10.3390/genes11050499] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 04/19/2020] [Accepted: 04/30/2020] [Indexed: 12/15/2022] Open
Abstract
Sarcomas are highly aggressive cancers that have a high propensity for metastasis, fail to respond to conventional therapies, and carry a poor 5-year survival rate. This is particularly true for patients with neurofibromatosis type 1 (NF1), in which 8%–13% of affected individuals will develop a malignant peripheral nerve sheath tumor (MPNST). Despite continued research, no effective therapies have emerged from recent clinical trials based on preclinical work. One explanation for these failures could be the lack of attention to intra-tumoral heterogeneity. Prior studies have relied on a single sample from these tumors, which may not be representative of all subclones present within the tumor. In the current study, samples were taken from three distinct areas within a single tumor from a patient with an NF1-MPNST. Whole exome sequencing, RNA sequencing, and copy number analysis were performed on each sample. A blood sample was obtained as a germline DNA control. Distinct mutational signatures were identified in different areas of the tumor as well as significant differences in gene expression among the spatially distinct areas, leading to an understanding of the clonal evolution within this patient. These data suggest that multi-regional sampling may be important for driver gene identification and biomarker development in the future.
Collapse
Affiliation(s)
- Chang-In Moon
- Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; (C.-I.M.); (Y.W.); (X.Z.)
| | - William Tompkins
- Washington University School of Medicine, St. Louis, MO 63110, USA;
| | - Yuxi Wang
- Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; (C.-I.M.); (Y.W.); (X.Z.)
| | - Abigail Godec
- College of Human Medicine, Michigan State University, East Lansing, MI 48824, USA;
| | - Xiaochun Zhang
- Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; (C.-I.M.); (Y.W.); (X.Z.)
| | - Patrik Pipkorn
- Department of Otolaryngology, Division of Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA;
- Siteman Cancer Center, St. Louis, MO 63110, USA; (C.A.M.); (S.D.)
| | - Christopher A. Miller
- Siteman Cancer Center, St. Louis, MO 63110, USA; (C.A.M.); (S.D.)
- McDonnell Genome Institute, Division of Oncology—Stem Cell Biology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
| | - Carina Dehner
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA;
| | - Sonika Dahiya
- Siteman Cancer Center, St. Louis, MO 63110, USA; (C.A.M.); (S.D.)
- Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA;
| | - Angela C. Hirbe
- Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; (C.-I.M.); (Y.W.); (X.Z.)
- Siteman Cancer Center, St. Louis, MO 63110, USA; (C.A.M.); (S.D.)
- Correspondence: ; Tel.: +1-314-747-3096
| |
Collapse
|
|
28
|
Lang N, Wang C, Zhao J, Shi F, Wu T, Cao H. Long non‑coding RNA BCYRN1 promotes glycolysis and tumor progression by regulating the miR‑149/PKM2 axis in non‑small‑cell lung cancer. Mol Med Rep 2020; 21:1509-1516. [PMID: 32016455 PMCID: PMC7003037 DOI: 10.3892/mmr.2020.10944] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2019] [Accepted: 12/16/2019] [Indexed: 12/23/2022] Open
Abstract
Cancer cells use aerobic glycolysis to sustain their proliferation. Long non‑coding RNA brain cytoplasmic RNA 1 (BCYRN1) has been reported to act as an oncogene in non‑small‑cell lung cancer (NSCLC). The present study investigated the role of BCYRN1 in NSCLC glycolysis. BCYRN1 expression was detected in NSCLC cells and tissues using reverse transcription‑quantitative PCR. The effect of BCYRN1 on aerobic glycolysis was examined by measuring NSCLC cell glucose catabolism and lactate synthesis. The relationships between BCYRN1 and microRNA (miR)‑149, and between miR‑149 and pyruvate kinase M1/2 (PKM2) were measured using a dual‑luciferase reporter assay. Cell proliferation and invasion were analyzed by the Cell Counting kit‑8 assay and the Matrigel invasion assay, respectively. High BCYRN1 expression was observed in NSCLC tissues and cells compared with the corresponding controls. BCYRN1 induced glycolysis and upregulated the expression levels of PKM2 in NSCLC cells. In addition, BCYRN1 regulated miR‑149 expression levels, and miR‑149 inhibitor rescued the effects of si‑BCYRN1 on glucose consumption and lactate production. miR‑149 knockdown significantly enhanced the expression of PKM2. Furthermore, PKM2 inhibition significantly reversed the effects of miR‑149 inhibitor on glucose catabolism and lactate synthesis. Furthermore, PKM2 was involved in NSCLC cell proliferation and invasion, and BCYRN1 knockdown and miR‑149 overexpression inhibited both processes. The present study suggested that BCYRN1 was involved in cell glycolysis, proliferation and invasion during NSCLC via regulating miR‑149 and PKM2.
Collapse
Affiliation(s)
- Ning Lang
- Department of Preventive Health, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
| | - Chunyang Wang
- Department of Thoracic Surgery, First Hospital of Qiqihar City, Qiqihar, Heilongjiang 161000, P.R. China
| | - Jiangyang Zhao
- Department of Thoracic Surgery, First Hospital of Qiqihar City, Qiqihar, Heilongjiang 161000, P.R. China
| | - Feng Shi
- Department of Respiratory Diseases, First Hospital of Qiqihar City, Qiqihar, Heilongjiang 161000, P.R. China
| | - Tong Wu
- Department of Respiratory Diseases, First Hospital of Qiqihar City, Qiqihar, Heilongjiang 161000, P.R. China
| | - Hongyan Cao
- Department of Oncology, First Hospital of Qiqihar City, Qiqihar, Heilongjiang 161000, P.R. China
| |
Collapse
|
|
29
|
Ding S, Jin Y, Hao Q, Kang Y, Ma R. LncRNA BCYRN1/miR-490-3p/POU3F2, served as a ceRNA network, is connected with worse survival rate of hepatocellular carcinoma patients and promotes tumor cell growth and metastasis. Cancer Cell Int 2020; 20:6. [PMID: 31920461 PMCID: PMC6945438 DOI: 10.1186/s12935-019-1081-x] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Accepted: 12/17/2019] [Indexed: 12/15/2022] Open
Abstract
Backgrounds LncRNA Brain Cytoplasmic RNA 1 (BCYRN1) has been certified to modulate cancer cells growth and aggressiveness in several tumors. However, research about function of BCYRN1 in hepatocellular carcinoma (HCC) is limited. Therefore, our research intends to explore the function of BCYRN1 in HCC. Methods HepG2 and BEL-7402 cell lines were employed for later function experiments. Differently expression levels of BCYRN1, miR-490-3p, and POU class 3 homeobox 2 (POU3F2) were determined on the base of TCGA dataset including 375 HCC patients and 50 normal. 370 cases of patients, which have fairly complete clinical data, were utilized for survival analysis of BCYRN1, miR-490-3p, or POU3F2 by Kaplan–Meier method. Relative expression pattern of BCYRN1 was examined by quantitative real time polymerase chain reaction (qRT-PCR), and relative expression level of POU3F2 was assessed by qRT-PCR and western blot. Cell biological behaviors were analyzed by cell counting kit-8, cloning formation, and transwell assays. Bioinformatics software and dual luciferase assay were applied to predict and confirm the targeted relationship between BCYRN1 and miR-490-3p, as well as miR-490-3p and POU3F2. Further associations among BCYRN1, miR-490-3p, and POU3F2 were analyzed by rescue assays. Results Our results exhibited that BCYRN1 was over expressed in HCC samples, which was connected with unfavorable prognosis in HCC patients. In addition, a series of experiments exhibited that overexpression of BCYRN1 significantly expedited HCC cells growth, clone formation, and movement abilities, and vice versa. Moreover, targeted relationships between BCYRN1 and miR-490-3p, as well as miR-490-3p and POU3F2 were affirmed by dual luciferase assay. Furthermore, POU3F2 expression was negatively connected with the expression of miR-490-3p and positively associated with BCYRN1 expression. Whilst, either overexpression of miR-490-3p or knockdown of POU3F2 could remarkably inhibit the increasing trends of proliferation, clone formation, invasion, and migration abilities induced by BCYRN1 in HCC cells. Conclusions BCYRN1, served as a competing endogenous RNA, up-regulated the expression of POU3F2 to promote the development of HCC through sponging miR-490-3p, supplying novel molecular targets and underlying prognostic biomarkers for HCC therapy.
Collapse
Affiliation(s)
- Shichao Ding
- Affiliated Hospital of Shandong Academy of Medical Sciences, Shandong First Medical University, Internal Second Medicine, Jinan, Shandong China
| | - Yanfeng Jin
- 2Department of Gastroenterology, Yantai Yuhuangding Hospital, Yantai, Shandong China
| | - Qingzhi Hao
- Department of Peripheral Vascular Diseases, The Affiliated Hospital of University of Traditional Chinese Medicine, Jinan, Shandong China
| | - Yanmeng Kang
- Department of Respiratory Diseases, The First Affiliated Hospital of Shandong First Medical University, Jinan, China.,5Department of Respiratory Diseases, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong China
| | - Ruiping Ma
- Department of Liver Diseases, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong China.,7Department of Liver Diseases, Shandong Provincial Qianfoshan Hospital, Shandong University, No. 16766, Jingshi Road, Jinan, 250000 Shandong China
| |
Collapse
|
|
30
|
Tan N, Zhu B, Shu H, Tao YF, Wu JR, Fang M, Li CR, Chen ZQ, Ou C. Effect of lncRNA‑BC200 on proliferation and migration of liver cancer cells in vitro and in vivo. Oncol Rep 2019; 43:461-470. [PMID: 31894342 PMCID: PMC6967153 DOI: 10.3892/or.2019.7447] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 11/08/2019] [Indexed: 12/25/2022] Open
Abstract
In recent years, the important role of long non‑coding RNAs (lncRNAs) in the development of liver cancer has received increasing attention. The abnormal expression level of long non‑coding RNAs has been associated with the occurrence and development of liver cancer. However, the role and molecular mechanisms of lncRNAs in the development and progression of liver cancer are not fully understood. The present study aimed to clarify the function and molecular mechanism of lncRNA brain cytoplasmic 200 (BC200) in liver cancer. In the present study, it was found that BC200 expression level was higher in hepatocellular carcinoma (HCC) tissues than that in adjacent tissues. Cell function was examined by constructing BC200 knockout (KO) and BC200‑overexpression in vitro models. It was found that BC200 affected the proliferation and migration of HepG2 cells. Interestingly, it was found that BC200 affected the expression of c‑Myc protein but did not affect the mRNA expression level of c‑MYC. BC200 KO cells exhibited a reduced protein expression level of Bax protein and an increased protein expression level of Bcl‑xL. Conversely, BC200 overexpression reduced the expression of Bcl‑xL protein and increased the expression of Bax protein. Importantly, it was found that BC200 affected the formation of subcutaneous tumors in nude mice. In conclusion, the present results suggested that lncRNA BC200 may play an important role in liver cancer.
Collapse
Affiliation(s)
- Ni Tan
- Department of Clinical Laboratory Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Bo Zhu
- Department of Clinical Laboratory Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Hong Shu
- Department of Clinical Laboratory Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Yi-Feng Tao
- Department of Clinical Laboratory Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Jun-Rong Wu
- Department of Clinical Laboratory Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Min Fang
- Department of Clinical Laboratory Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Chun-Rong Li
- Department of Clinical Laboratory Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Zhong-Qing Chen
- Department of Clinical Laboratory Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| | - Chao Ou
- Department of Clinical Laboratory Medicine, The Affiliated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi 530021, P.R. China
| |
Collapse
|
|
31
|
Jing H, Liu L, Jia Y, Yao H, Ma F. Overexpression of the long non-coding RNA Oprm1 alleviates apoptosis from cerebral ischemia-reperfusion injury through the Oprm1/miR-155/GATA3 axis. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2019; 47:2431-2439. [PMID: 31187646 DOI: 10.1080/21691401.2019.1626408] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Numerous differentially expressed long non-coding RNAs (lncRNAs) have been identified in cerebral ischemia-reperfusion (I/R) injury using RNA-Seq analysis. However, little is known about whether and how lncRNAs are involved in cerebral I/R injury. In this study, we investigated the function of the lncRNA Oprm1 in cerebral I/R injury and explored the underlying mechanism. An oxygen-glucose deprivation model in N2a cells was utilized to mimic cerebral I/R injury in vitro. Trypan blue staining, terminal deoxytransferase-mediated dUTP-biotin nick end labelling and caspase-3 were measured to evaluate apoptosis. Middle cerebral artery occlusion was performed in mice to evaluate the function of lncRNA Oprm1 in vivo. Real-time PCR and western blotting were used to measure the expression levels of lncRNA Opmr1, caspase-3, miR-155, GATA binding protein 3 (GATA3) and nuclear factor (NF)-κB. lncRNA Oprm1 was mainly located in the cytoplasm. Overexpression of lncRNA Oprm1 alleviated the apoptosis induced by oxygen-glucose deprivation and significantly reduced cleaved caspase-3 levels. Infarct size was distinctly decreased in the lncRNA Oprm1-overexpression group. The neurological score was also improved. Our findings showed that the lncRNA Oprm1/miR-155/GATA3 axis plays an important role in cerebral I/R injury. lncRNA Oprm1 may attenuate cerebral injury through the NF-κB pathway. lncRNA Oprm1 may serve as a potential target for new therapeutic interventions in patients with ischemic stroke.
Collapse
Affiliation(s)
- Hongyu Jing
- a Department of Respiratory Medicine, First Hospital of Jilin University , Changchun , China
| | - Lingyun Liu
- b Department of Andrology, First Hospital of Jilin University , Changchun , China
| | - Ye Jia
- c Department of Nephrology, First Hospital of Jilin University , Changchun , China
| | - Hanxin Yao
- d Department of Clinical Laboratory, First Hospital of Jilin University , Changchun , China
| | - Fuzhe Ma
- c Department of Nephrology, First Hospital of Jilin University , Changchun , China
| |
Collapse
|
|
32
|
Ming XL, Feng YL, He DD, Luo CL, Rong JL, Zhang WW, Ye P, Chai HY, Liang CZ, Tu JC. Role of BCYRN1 in hepatocellular carcinoma pathogenesis by lncRNA-miRNA-mRNA network analysis and its diagnostic and prognostic value. Epigenomics 2019; 11:1209-1231. [PMID: 31339046 DOI: 10.2217/epi-2018-0218] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Aim: This study aimed to excavate the roles of BCYRN1 in hepatocellular carcinoma (HCC). Methods: A comprehensive strategy of microarray data mining, computational biology and experimental verification were adopted to assess the clinical significance of BCYRN1 and identify related pathways. Results: BCYRN1 was upregulated in HCC and its expression was positively associated with both tumor, node, metastasis and worse survival rate in patients with HCC. Through combing plasma BCYRN1 with alpha fetoprotein, the diagnosis of HCC was remarkably improved. BCYRN1 may regulate some cancer-related pathways to promote HCC initiation via an lncRNA-miRNA-mRNA network. Conclusion: Our results propose BCYRN1 as a potential diagnostic and prognostic biomarker and offer a novel perspective to explore the etiopathogenesis of HCC.
Collapse
Affiliation(s)
- Xin-Liang Ming
- Department & Program of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China
| | - Yan-Lin Feng
- Department & Program of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China
| | - Ding-Dong He
- Department & Program of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China
| | - Chang-Liang Luo
- Department & Program of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China
| | - Jia-Ling Rong
- Department & Program of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China
| | - Wu-Wen Zhang
- Department & Program of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China
| | - Peng Ye
- Department & Program of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China
| | - Hong-Yan Chai
- Department & Program of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China
| | - Chun-Zi Liang
- Department & Program of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China
| | - Jian-Cheng Tu
- Department & Program of Clinical Laboratory Medicine, Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan 430071, PR China
| |
Collapse
|
|
33
|
Zhen Y, Ye Y, Wang H, Xia Z, Wang B, Yi W, Deng X. Knockdown of SNHG8 repressed the growth, migration, and invasion of colorectal cancer cells by directly sponging with miR-663. Biomed Pharmacother 2019; 116:109000. [PMID: 31152930 DOI: 10.1016/j.biopha.2019.109000] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2019] [Revised: 05/11/2019] [Accepted: 05/14/2019] [Indexed: 11/18/2022] Open
Abstract
Aberrant expression of SNHG8 has been observed in some types of cancers. However, whether SNHG8 was aberrantly expressed in colorectal cancer and whether it could exert any function on the development of colorectal cancer remains largely elusive. In this study, we first investigated the expression pattern and biological function of SNHG8 in colorectal cancer. The expression level of SNHG8 was investigated in colorectal cancer tissues as well as in colorectal cancer cell lines by real-time PCR. Next, CCK8 assays were performed to evaluate the effects of SNHG8 on the proliferation of colorectal cancer cells and transwell assays were employed to evaluate migration and invasion. Bioinformatics were used for predicting the sponging miRNAs that interact with SNHG8. A dual luciferase reporter assay was adopted for the verification of interaction between SNHG8 and miRNA. Our data showed that SNHG8 was significantly up-regulated in colorectal cancer tissues and cell lines. In addition, knockdown of SNHG8 significantly inhibited the growth, migration, and invasion of colorectal cancer cells. It was predicted that miR-663 might interact with SNHG8 and the direct sponging was verified by dual luciferase reporter assay. Moreover, rescue experiments revealed that SNHG8 played a tumor promoting role by regulating miR-663. In the present study, we revealed that SNHG8 was up-regulated in colorectal cancer and promoted the proliferation, migration, and invasion of colorectal cancer by sponging miR-663, which helps to further reveal the underlying developmental mechanism of action and provides a potential therapeutic molecule for colorectal cancer therapy in the future.
Collapse
Affiliation(s)
- Yan Zhen
- Department of Integrative Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangzhou, China
| | - Yushan Ye
- Department of Stomatology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Huajun Wang
- Department of Digestive internal medicine, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou, China
| | - ZhongSheng Xia
- Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China
| | - Bei Wang
- Department of Care Zone 3, Guangdong Academy of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou, China
| | - Weimin Yi
- Department of Integrative Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangzhou, China.
| | - Xiaoyan Deng
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
| |
Collapse
|
|
34
|
Huang W, Zhou R, Mao L, Deng C, Dang X. Esophageal cancer related gene-4 inhibits the migration and proliferation of oral squamous cell carcinoma through BC200 lncRNA/MMP-9 and -13 signaling pathway. Cell Signal 2019; 62:109327. [PMID: 31152845 DOI: 10.1016/j.cellsig.2019.05.012] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 05/21/2019] [Accepted: 05/26/2019] [Indexed: 12/22/2022]
Abstract
Esophageal cancer related gene-4 (ECRG4) inhibits the malignant phenotype of oral squamous cell carcinoma. However, the molecular mechanisms remain to be explored. Using the tongue carcinoma cell line, TCA8113 as a cell model, we showed that forced expression of ECRG4 down-regulated the expression of the BC200 long non-coding RNA (lncRNA) and matrix metalloproteinases (MMP-9 and MMP-13). Restoration of BC200 lncRNA rescued ECRG4-mediated down-regulation of MMP-9 and -13. Furthermore, over-expression of Ecrg4 inhibited cell proliferation and migration, which was abolished by forced expression of BC200 lncRNA in TCA8113 cells. Our results indicate that ECRG4 inhibits the malignant phenotype of TCA8113 cells most likely through suppression of BC200 lncRNA/MMPs signaling pathway, rationalizing that BC200 lncRNA may be a potential target for oral squamous cell carcinoma (OSCC) therapy.
Collapse
Affiliation(s)
- Wenjun Huang
- The Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Rui Zhou
- The Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Liang Mao
- The Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Chenliang Deng
- Department of Plastic Surgery, Shanghai 6th People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200237, China.
| | - Xitong Dang
- The Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan 646000, China.
| |
Collapse
|
|
35
|
Xuan P, Cao Y, Zhang T, Kong R, Zhang Z. Dual Convolutional Neural Networks With Attention Mechanisms Based Method for Predicting Disease-Related lncRNA Genes. Front Genet 2019; 10:416. [PMID: 31130990 PMCID: PMC6509943 DOI: 10.3389/fgene.2019.00416] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2019] [Accepted: 04/16/2019] [Indexed: 12/30/2022] Open
Abstract
A lot of studies indicated that aberrant expression of long non-coding RNA genes (lncRNAs) is closely related to human diseases. Identifying disease-related lncRNAs (disease lncRNAs) is critical for understanding the pathogenesis and etiology of diseases. Most of the previous methods focus on prioritizing the potential disease lncRNAs based on shallow learning methods. The methods fail to extract the deep and complex feature representations of lncRNA-disease associations. Furthermore, nearly all the methods ignore the discriminative contributions of the similarity, association, and interaction relationships among lncRNAs, disease, and miRNAs for the association prediction. A dual convolutional neural networks with attention mechanisms based method is presented for predicting the candidate disease lncRNAs, and it is referred to as CNNLDA. CNNLDA deeply integrates the multiple source data like the lncRNA similarities, the disease similarities, the lncRNA-disease associations, the lncRNA-miRNA interactions, and the miRNA-disease associations. The diverse biological premises about lncRNAs, miRNAs, and diseases are combined to construct the feature matrix from the biological perspectives. A novel framework based on the dual convolutional neural networks is developed to learn the global and attention representations of the lncRNA-disease associations. The left part of the framework exploits the various information contained by the feature matrix to learn the global representation of lncRNA-disease associations. The different connection relationships among the lncRNA, miRNA, and disease nodes and the different features of these nodes have the discriminative contributions for the association prediction. Hence we present the attention mechanisms from the relationship level and the feature level respectively, and the right part of the framework learns the attention representation of associations. The experimental results based on the cross validation indicate that CNNLDA yields superior performance than several state-of-the-art methods. Case studies on stomach cancer, lung cancer, and colon cancer further demonstrate CNNLDA's ability to discover the potential disease lncRNAs.
Collapse
Affiliation(s)
- Ping Xuan
- School of Computer Science and Technology, Heilongjiang University, Harbin, China
| | - Yangkun Cao
- School of Computer Science and Technology, Heilongjiang University, Harbin, China
| | - Tiangang Zhang
- School of Mathematical Science, Heilongjiang University, Harbin, China
| | - Rui Kong
- Department of Pancreatic and Biliary Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Zhaogong Zhang
- School of Computer Science and Technology, Heilongjiang University, Harbin, China
| |
Collapse
|
|
36
|
Liu Y, Feng X, Zhao H, Xuan Z, Wang L. A Novel Network-Based Computational Model for Prediction of Potential LncRNA⁻Disease Association. Int J Mol Sci 2019; 20:ijms20071549. [PMID: 30925672 PMCID: PMC6480945 DOI: 10.3390/ijms20071549] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 03/22/2019] [Accepted: 03/25/2019] [Indexed: 12/12/2022] Open
Abstract
Accumulating studies have shown that long non-coding RNAs (lncRNAs) are involved in many biological processes and play important roles in a variety of complex human diseases. Developing effective computational models to identify potential relationships between lncRNAs and diseases can not only help us understand disease mechanisms at the lncRNA molecular level, but also promote the diagnosis, treatment, prognosis, and prevention of human diseases. For this paper, a network-based model called NBLDA was proposed to discover potential lncRNA⁻disease associations, in which two novel lncRNA⁻disease weighted networks were constructed. They were first based on known lncRNA⁻disease associations and topological similarity of the lncRNA⁻disease association network, and then an lncRNA⁻lncRNA weighted matrix and a disease⁻disease weighted matrix were obtained based on a resource allocation strategy of unequal allocation and unbiased consistence. Finally, a label propagation algorithm was applied to predict associated lncRNAs for the investigated diseases. Moreover, in order to estimate the prediction performance of NBLDA, the framework of leave-one-out cross validation (LOOCV) was implemented on NBLDA, and simulation results showed that NBLDA can achieve reliable areas under the ROC curve (AUCs) of 0.8846, 0.8273, and 0.8075 in three known lncRNA⁻disease association datasets downloaded from the lncRNADisease database, respectively. Furthermore, in case studies of lung cancer, leukemia, and colorectal cancer, simulation results demonstrated that NBLDA can be a powerful tool for identifying potential lncRNA⁻disease associations as well.
Collapse
Affiliation(s)
- Yang Liu
- College of Computer Engineering & Applied Mathematics, Changsha University, Changsha 410000, China.
- Key Laboratory of Hunan Province for Internet of Things and Information Security, Xiangtan University, Xiangtan 411100, China.
| | - Xiang Feng
- College of Computer Engineering & Applied Mathematics, Changsha University, Changsha 410000, China.
- Key Laboratory of Hunan Province for Internet of Things and Information Security, Xiangtan University, Xiangtan 411100, China.
| | - Haochen Zhao
- Key Laboratory of Hunan Province for Internet of Things and Information Security, Xiangtan University, Xiangtan 411100, China.
| | - Zhanwei Xuan
- Key Laboratory of Hunan Province for Internet of Things and Information Security, Xiangtan University, Xiangtan 411100, China.
| | - Lei Wang
- College of Computer Engineering & Applied Mathematics, Changsha University, Changsha 410000, China.
- Key Laboratory of Hunan Province for Internet of Things and Information Security, Xiangtan University, Xiangtan 411100, China.
| |
Collapse
|
|
37
|
Su P, Mu S, Wang Z. Long Noncoding RNA SNHG16 Promotes Osteosarcoma Cells Migration and Invasion via Sponging miRNA-340. DNA Cell Biol 2019; 38:170-175. [PMID: 30726150 DOI: 10.1089/dna.2018.4424] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Long noncoding RNA host gene 16 (SNHG16) has a key role in a variety of cancer progression. However, the role and mechanism of SNHG16 in osteosarcoma (OS) remain unknown. In this study, we examined the functional role of SNHG16 in OS cells through knocked-down SNHG16 by using siRNA. We found that SNHG16 is overexpressed in OS tissues and cell lines. Inhibition of SNHG16 reduced OS cells proliferation, stimulated apoptosis, and decreased migration and invasion. In addition, SNHG16 reduced miR-340 expression in OS cells. The results showed that SNHG16 involves in the migration and invasion of OS cells through sponging miRNA-340. Together, our data support an important role of SNHG16 in regulating OS cell invasion and migration that highlights SNHG16 may be regarded as a potential target for OS treatment.
Collapse
Affiliation(s)
- Pan Su
- 1 Luoyang Orthopedic Hospital of Henan Province, Orthopedic Hospital of Henan Province, Henan, China
| | - Shimin Mu
- 1 Luoyang Orthopedic Hospital of Henan Province, Orthopedic Hospital of Henan Province, Henan, China
| | - Zhiyuan Wang
- 2 Department of Orthopedics, Tongji Hospital, Tongji University School of Medicine, Shanghai, China
| |
Collapse
|
|
38
|
A novel lncRNA LOC101927746 accelerates progression of colorectal cancer via inhibiting miR-584-3p and activating SSRP1. Biochem Biophys Res Commun 2019; 509:734-738. [PMID: 30616889 DOI: 10.1016/j.bbrc.2018.12.174] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Accepted: 12/27/2018] [Indexed: 12/15/2022]
Abstract
An increasing number of reports have indicated that long noncoding RNAs (lncRNAs) are involved in the pathogenesis of colorectal cancer (CRC). However, many lncRNAs remain unidentified in CRC, and their functions are yet to be elucidated. In this study, we investigated the function of lncRNA LOC101927746 in CRC progression. We found that LOC101927746 expression was significantly increased in CRC tissues according to the GEO dataset. Moreover, LOC101927746 expression was positively correlated with tumor stage and metastasis. Additionally, the high expression of LOC101927746 predicted poor prognosis in CRC patients. Functionally, we demonstrated that LOC101927746 silencing significantly suppressed the proliferation, migration, and invasion of CRC cells. In terms of its mechanism, LOC101927746 could serve as a competing endogenous RNA to inhibit miR-584-3p and activate its target gene SSRP1. The expression of miR-584-3p was inversely correlated with either LOC101927746 or SSRP1 in CRC tissues. The overexpression of SSRP1 or inhibition of miR-584-3p could reverse the effects of LOC101927746 knockdown in CRC cells. Taken together, our results suggest that the LOC101927746/miR-584-3p/SSRP1 axis modulates CRC progression.
Collapse
|
|
39
|
Yang H, Jin L, Sun X. A thirteen‑gene set efficiently predicts the prognosis of glioblastoma. Mol Med Rep 2019; 19:1613-1621. [PMID: 30628650 PMCID: PMC6390043 DOI: 10.3892/mmr.2019.9801] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2018] [Accepted: 09/06/2018] [Indexed: 12/13/2022] Open
Abstract
Glioblastoma multiforme (GBM) is the most common type of brain cancer; it usually recurs and patients have a short survival time. The present study aimed to construct a gene expression classifier and to screen key genes associated with GBM prognosis. GSE7696 microarray data set included samples from 10 recurrent GBM tissues, 70 primary GBM tissues and 4 normal brain tissues. Seed genes were identified by the 'survival' package in R and subjected to pathway enrichment analysis. Prognostic genes were selected from the seed genes using the 'rbsurv' package in R, unsupervised hierarchical clustering, survival analysis and enrichment analysis. Multivariate survival analysis was performed for the prognostic genes, and the GBM data set from The Cancer Genome Atlas database was utilized to validate the prognostic genes. Of the 1,785 seed genes analyzed, 13 prognostic feature genes, including collagen type XXVIII α1 chain (COL28A1), PDS5 cohesin‑associated factor A (PDS5A), zinc‑finger DHHC‑type containing 2 (ZDHHC2), zinc‑finger protein 24 (ZNF24), myosin VA (MYO5A) and myeloid/lymphoid or mixed‑lineage leukemia translocated to 4 (MLLT4), were identified. These genes performed well on sample classification and prognostic risk differentiation, and six pathways, including adherens junction, cyclic adenosine 3',5'‑monophosphate signaling and Ras signaling pathways, were enriched for these feature genes. The high‑risk group was slightly older compared with the low‑risk group. The validation data set confirmed the prognostic value of the 13 feature genes for GBM; of these, COL28A1, PDS5A, ZDHHC2, ZNF24, MYO5A and MLLT4 may be crucial. These results may aid the understanding of the pathogenesis of GBM and provide important clues for the development of novel diagnostic markers or therapeutic targets.
Collapse
Affiliation(s)
- Huyin Yang
- Department of Neurosurgery, Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
| | - Luhao Jin
- Department of Neurosurgery, Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
| | - Xiaoyang Sun
- Department of Neurosurgery, Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
| |
Collapse
|
|
40
|
Shin H, Kim Y, Kim M, Lee Y. BC200 RNA: An Emerging Therapeutic Target and Diagnostic Marker for Human Cancer. Mol Cells 2018; 41:993-999. [PMID: 30590906 PMCID: PMC6315322 DOI: 10.14348/molcells.2018.0425] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 11/14/2018] [Indexed: 12/17/2022] Open
Abstract
One of the most interesting findings from genome-wide expression analysis is that a considerable amount of noncoding RNA (ncRNA) is present in the cell. Recent studies have identified diverse biological functions of ncRNAs, which are expressed in a much wider array of forms than proteins. Certain ncRNAs associated with diseases, in particular, have attracted research attention as novel therapeutic targets and diagnostic markers. BC200 RNA, a 200-nucleotide ncRNA originally identified as a neuron-specific transcript, is abnormally over-expressed in several types of cancer tissue. A number of recent studies have suggested mechanisms by which abnormal expression of BC200 RNA contributes to the development of cancer. In this article, we first provide a brief review of a recent progress in identifying functions of BC200 RNA in cancer cells, and then offer examples of other ncRNAs as new therapeutic targets and diagnostic markers for human cancer. Finally, we discuss future directions of studies on BC200 RNA for new cancer treatments.
Collapse
Affiliation(s)
- Heegwon Shin
- Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141,
Korea
| | - Youngmi Kim
- Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141,
Korea
| | - Meehyein Kim
- Virus Research and Testing Group, Korea Research Institute of Chemical Technology, Daejeon 34114,
Korea
| | - Younghoon Lee
- Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141,
Korea
| |
Collapse
|
|
41
|
ELK1-induced upregulation of long non-coding RNA MIR100HG predicts poor prognosis and promotes the progression of osteosarcoma by epigenetically silencing LATS1 and LATS2. Biomed Pharmacother 2018; 109:788-797. [PMID: 30551532 DOI: 10.1016/j.biopha.2018.10.029] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Revised: 09/21/2018] [Accepted: 10/04/2018] [Indexed: 11/21/2022] Open
Abstract
Osteosarcoma (OS) is the commonest malignant bone tumor in the world. High incidence of OS has gradually become a social problem. Recent years, numerous studies have revealed that long non-coding RNAs (lncRNAs) are crucial regulators in the tumor progression. As a member of lncRNA family, MIR100HG has been reported to be an oncogene in breast cancer and acute megakaryoblastic leukemia. Nevertheless, the specific role of MIR100HG in osteosarcoma is still unclear. In this study, we investigated the biological function and molecular mechanism of MIR100HG in the progression of osteosarcoma. At first, we measured the high expression of MIR100HG in OS tissues and cell lines by qRT-PCR. Kaplan-Meier method revealed that high expression of MIR100HG is a factor for the poor prognosis of OS patients (P = 0.004). To explore the effect of MIR100HG on the biological processes of OS, loss-of-function assays were conducted in OS cells. Functionally, MIR100HG knockdown suppressed cell proliferation, cell cycle progression while promoted cell apoptosis. Mechanistically, MIR100HG was upregulated by the transcription factor ELK1. The upregulation of MIR100HG led to the inactivation of Hippo pathway. Furthermore, we found that MIR100HG inactivated Hippo pathway in OS cells by epigenetically silencing LATS1 and LATS2. Rescue assays demonstrated that LATS1/2 involved in MIR100HG-mediated OS progression. In summary, our study indicated that ELK1-induced upregulation of MIR100HG promoted OS progression by epigenetically silencing LATS1 and LATS2 and inactivating Hippo pathway.
Collapse
|