GAS5 long non-coding RNA in malignant pleural mesothelioma (original) (raw)
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Background: GAS5 is expressed in growth arrested cells as a result of nutrient deprivation or growth factor withdrawal. Besides its roles in metabolism, GAS5 has been studied in a variety of human cancers. The aim of the present work was to review the literature and report all recent findings of the roles of GAS5 in a variety of tumors. Methods: An electronic literature search was conducted by the authors using the keywords "GAS5" and "cancer", and then individually searched for each type of cancer that was brought up by the first search. Original articles and systematic reviews were selected, and the titles and abstracts of the papers were screened to determine whether they met the eligibility criteria. In addition, we performed computer-based structural analysis on the human GAS5 RNA for extending our understanding on its biological and/or pathological actions. Results: We have found that the majority of studies, irrespectively of tumor types, confirm the role of GAS5 as a tumor suppressor gene. Especially, more recent findings have also highlighted GAS5 interaction with miRNAs contributing even more to its tumor inhibiting role. In particular, we could outline two miRNAs, which came up throughout our review; miR-222 and miR-21. GAS5, miR-222 and miR-21 could pose potential prognostic and diagnostic biomarkers for a variety of tumors, making them quite useful in cancer clinic. Conclusions: For certain, more studies are required in order to better understand the role of GAS5 in tumor biology, and in particular the signaling pathways in which the gene participates.
Tumor Suppressive Effects of GAS5 in Cancer Cells
Non-Coding RNA
In recent years, long non-coding RNAs (lncRNAs) have been shown to play important regulatory roles in cellular processes. Growth arrests specific transcript 5 (GAS5) is a lncRNA that is highly expressed during the cell cycle arrest phase but is downregulated in actively growing cells. Growth arrests specific transcript 5 was discovered to be downregulated in several cancers, primarily solid tumors, and it is known as a tumor suppressor gene that regulates cell proliferation, invasion, migration, and apoptosis via multiple molecular mechanisms. Furthermore, GAS5 polymorphism was found to affect GAS5 expression and functionality in a cell-specific manner. This review article focuses on GAS5’s tumor-suppressive effects in regulating oncogenic signaling pathways, cell cycle, apoptosis, tumor-associated genes, and treatment-resistant cells. We also discussed genetic polymorphisms of GAS5 and their association with cancer susceptibility.
Long non-coding RNA GAS5 regulates apoptosis in prostate cancer cell lines
Biochimica et biophysica acta, 2013
While the role of small non-coding RNAs, such as miRNAs, in apoptosis control is well established, long non-coding RNAs (lncRNAs) have received less attention. Growth Arrest-Specific 5 (GAS5) encodes multiple snoRNAs within its introns, while exonic sequences produce lncRNA which can act as a riborepressor of the glucocorticoid and related receptors. GAS5 negatively regulates the survival of lymphoid and breast cells, and is aberrantly expressed in several cancers. Although cellular GAS5 levels decline as prostate cancer cells acquire castration-resistance, the influence of GAS5 on prostate cell survival has not been determined. To address this question, prostate cell lines were transfected with GAS5-encoding plasmids or GAS5 siRNAs, and cell survival was assessed. Basal apoptosis increased, and cell survival decreased, after transfection of 22Rv1 cells with plasmids encoding GAS5 transcripts, including mature GAS5 lncRNA. Similar effects were observed in PC-3 cells. In stable clone...
The Non-Coding RNA GAS5 and Its Role in Tumor Therapy-Induced Resistance
International Journal of Molecular Sciences
The growth arrest-specific transcript 5 (GAS5) is a >200-nt lncRNA molecule that regulates several cellular functions, including proliferation, apoptosis, invasion and metastasis, across different types of human cancers. Here, we reviewed the current literature on the expression of GAS5 in leukemia, cervical, breast, ovarian, prostate, urinary bladder, lung, gastric, colorectal, liver, osteosarcoma and brain cancers, as well as its interaction with various miRNAs and its effect on therapy-related resistance in these malignancies. The general consensus is that GAS5 acts as a tumor suppressor across different tumor types and that its up-regulation results in tumor sensitization to chemotherapy or radiotherapy. GAS5 seems to play a previously unappreciated, but significant role in tumor therapy-induced resistance.
Journal of Biological Chemistry, 2015
Background: Long non-coding RNAs function as competing endogenous RNAs (ceRNAs). Whether growth arrest-specific transcript 5 (GAS5) acts as a ceRNA for microRNA-222 in liver fibrosis remains undefined. Results: GAS5 increases p27 expression as a ceRNA for microRNA-222, thereby inhibiting liver fibrosis progression. Conclusion: The GAS5/microRNA-222/p27 axis underlies the pathogenesis of liver fibrosis. Significance: The ceRNA network helps to understand liver fibrogenesis. Effective control of hepatic stellate cell (HSC) activation and proliferation is critical to the treatment of liver fibrosis. Long non-coding RNAs have been shown to play a pivotal role in the regulation of cellular processes. It has been reported that growth arrest-specific transcript 5 (GAS5) acts as a crucial mediator in the control of cell proliferation and growth. However, little is known about the role and underlying mechanism of GAS5 in liver fibrosis. In this study, our results indicated that GAS5 expression was reduced in mouse, rat, and human fibrotic liver samples and in activated HSCs. Overexpression of GAS5 suppressed the activation of primary HSCs in vitro and alleviated the accumulation of collagen in fibrotic liver tissues in vivo. We identified GAS5 as a target of microRNA-222 (miR-222) and showed that miR-222 could inhibit the expression of GAS5. Interestingly, GAS5 could also repress miR-222 expression. A pulldown assay further validated that GAS5 could directly bind to miR-222. As a competing endogenous RNAs, GAS5 had no effect on primary miR-222 expression. In addition, GAS5 was mainly localized in the cytoplasm. Quantitative RT-PCR further demonstrated that the copy numbers of GAS5 per cell are higher than those of miR-222. GAS5 increased the level of p27 protein by functioning as a competing endogenous RNA for miR-222,
Oncology and Translational Medicine, 2022
Objective Long non-coding RNAs (lncRNAs) regulate tumor development and progression by promoting tumor proliferation, invasion, and metastasis. The aim of the study was to investigate the effects of lncRNA growth arrest-special 5 (GAS5) on proliferation and apoptosis of hepatocellular carcinoma (HCC) cells through miR-26a-5p action. Methods Expression levels of GAS5 were detected in cancerous and paracancerous tissue of 80 HCC patients by RT-qPCR. The starBase tool predicted that GAS5 had binding sites for the miRNA miR-26a-5p, which was also highly expressed in HCC tissue. The relationship between GAS5 and miR-26a-5p was confirmed using a luciferase reporter assay. The role of these lncRNAs was further explored by transfecting plasmids into SMMC-7721 cells and classifying the cells as follows: NC group, GAS5 group, anti-miR-26a-5p group, and GAS5 + miR-26a-5p group. Cell proliferation, cell cycle, and apoptosis were detected in each group. The relationship between miR-26a-5p and phosphatase and tensin homolog deleted on chromosome 10 (PTEN) was analyzed by TargetScan database prediction and luciferase reporter assay. Western blotting was used to quantify PTEN, phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (p-Akt), cyclin D1, and human P27 protein (P27). Results GAS5 was downregulated, while miR-26a-5p was upregulated in HCC tissue compared to in paracancerous tissue. High GAS5 levels and low miR-26a-5p levels inhibited cell proliferation, increased the number of G0/G1 phase cells, promoted cell apoptosis, promoted PTEN and P27 expression, and inhibited PI3K, P-Akt, and cyclin D1 expression at the protein level. Upregulation of miR-26a-5p attenuated the effects of GAS5 upregulation on the proliferation, cell cycle, and apoptosis of HCC cells and on the expression of PTNE/PI3K/Akt signaling pathway-related proteins. Conclusion Low GAS5 levels regulate the proliferation and apoptosis of HCC cells via the PTNE/PI3K/ Akt signaling pathway and are linked to upregulation of miR-26a-5p.
GAS5, a non-protein-coding RNA, controls apoptosis and is downregulated in breast cancer
Oncogene, 2009
Effective control of both cell survival and cell proliferation is critical to the prevention of oncogenesis and to successful cancer therapy. Using functional expression cloning, we have identified GAS5 (growth arrest-specific transcript 5) as critical to the control of mammalian apoptosis and cell population growth. GAS5 transcripts are subject to complex post-transcriptional processing and some, but not all, GAS5 transcripts sensitize mammalian cells to apoptosis inducers. We have found that, in some cell lines, GAS5 expression induces growth arrest and apoptosis independently of other stimuli. GAS5 transcript levels were significantly reduced in breast cancer samples relative to adjacent unaffected normal breast epithelial tissues. The GAS5 gene has no significant protein-coding potential but expression encodes small nucleolar RNAs (snoRNAs) in its introns. Taken together with the recent demonstration of tumor suppressor characteristics in the related snoRNA U50, our observations suggest that such snoRNAs form a novel family of genes controlling oncogenesis and sensitivity to therapy in cancer.
Journal of Cellular Biochemistry, 2019
Genetic studies on cancers have revealed that lncRNA-GAS5 and lncRNA-FAL1 are overexpressed in some cancerous cells. The aim of the present investigation was to evaluate the roles of lncRNA-GAS5 and lncRNA-FAL1 gene expression changes in the diagnosis and prognosis of patients with papillary thyroid carcinoma (PTC). In a case-control investigation, we recruited a total of 140 formalin-fixed paraffin-embedded tissues of PTC, including 70 cancerous and noncancerous tissues. Quantitative real-time polymerase chain reaction was used to determine the lncRNA-GAS5 and lncRNA-FAL1 level of gene expression in the two tissue groups. The association between the clinicopathological characteristics of patients and the expression level of lncRNA-GAS5 and lncRNA-FAL1 was evaluated. Our findings revealed that the level of expression in the lncRNA-GAS5 and lncRNA-FAL1 genes was significantly upregulated in thyroid cancerous tissues (P < 0.003 and P < 0.040, respectively). The expression of lncRNA-GAS5 and lncRNA-FAL1 revealed a significant association with tumor node metastasis staging (P < 0.042 and P < 0.001, respectively). It seems that the lncRNA-GAS5 and lncRNA-FAL1 genes play an oncogenic role in PTC. The two genes have a significant potential prognostic value and may likely be used as novel therapeutic targets for PTC patients in the future.
2018
Accumulating evidence indicates that non-coding RNAs including microRNAs (miRs) and long non-coding RNAs (lncRNAs) are aberrantly expressed in cancer, providing promising biomarkers for diagnosis, prognosis and/or therapeutic targets. We aimed in the current work to quantify the expression profile of miR-34a and one of its bioinformatically selected partner lncRNA growth arrest-specific 5 (GAS5) in a sample of Egyptian cancer patients, including three prevalent types of cancer in our region; renal cell carcinoma (RCC), hepatocellular carcinoma (HCC) and glioblastoma (GB) as well as to correlate these expression profiles with the available clinicopathological data in an attempt to clarify their roles in cancer. Quantitative real-time polymerase chain reaction analysis was applied. Different bioinformatics databases were searched to confirm the potential miRNAs-lncRNA interactions of the selected ncRNAs in cancer pathogenesis. GAS5 was significantly under-expressed in the three types ...
Journal of biomedical science, 2018
LncRNA Gas5 is known to be a key control element during growth, differentiation and development in mammalian species. However, the role and function of Gas5 in growth plate chondrocytes has not been determined. The overexpression and knockdown models of Gas5 and miR-21 in cells and animals were constructed. Cell survival was determined by MTT assay and flow cytometry. Animal biochemical indices were measured by enzyme-linked immunosorbent assay, hematoxylin/eosin staining, immunohistochemistry or in situ hybridisation. Dual luciferase reporter gene assay was carried out to study targeting. First, we found the expression levels of fibroblast growth factor 1(FGF1) were up-regulated and miR-21 were down-regulated in Gas5 overexpressing model cells. Meanwhile, the expression levels of FGF1 and Gas5 were up-regulated in miR-21 knockdown model cells. Furthermore, cell proliferation was significantly promoted after Gas5 knockdown or miR-21 overexpression. Subsequently, Gas5 promoted apopto...