Dataset Information

Downregulation of GAS5 promotes bladder cancer cell proliferation, partly by regulating CDK6.

ABSTRACT:

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Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes, such as transcriptional regulation, cell growth and tumorigenesis. However, little is known about whether lncRNA-GAS5 (growth arrest-specific 5) regulates bladder cancer progression. In the present study, we found that the GAS5 expression is commonly downregulated in bladder cancer cell lines and human specimens. Knockdown of GAS5 promotes bladder cancer cell proliferation, whereas forced expression of GAS5 suppresses cell proliferation. We further demonstrated that knockdown of GAS5 increases CDK6 mRNA and protein levels in bladder cancer cells. Expectedly, GAS5 inhibition induces a significant decrease in G0/G1 phase and an obvious increase in S phase. Gain-of-function and loss-of-function studies showed that GAS5 inhibits bladder cancer cell proliferation, at least in part, by regulating CDK6 expression.

Conclusions

Downregulated GAS5 promotes bladder cancer cell proliferation, partly by regulating CDK6, and thus may be helpful in the development of effective treatment strategies against bladder cancer.

SUBMITTER: Liu Z

PROVIDER: S-EPMC3775789 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Downregulation of GAS5 promotes bladder cancer cell proliferation, partly by regulating CDK6.

Liu Zhihong Z Wang Wei W Jiang Juntao J Bao Erdun E Xu Dongliang D Zeng Yigang Y Tao Le L Qiu Jianxin J

PloS one 20130917 9

<h4>Unlabelled</h4>Long non-coding RNAs (lncRNAs) play important roles in diverse biological processes, such as transcriptional regulation, cell growth and tumorigenesis. However, little is known about whether lncRNA-GAS5 (growth arrest-specific 5) regulates bladder cancer progression. In the present study, we found that the GAS5 expression is commonly downregulated in bladder cancer cell lines and human specimens. Knockdown of GAS5 promotes bladder cancer cell proliferation, whereas forced expr ...[more]

PMID: 24069260

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Project description:The purpose of our study is to elucidate the expression of lncRNA00518 (lnc00518) in the bladder cancer, and its potential mechanism in regulating the development of bladder cancer. The expression of lnc00518 in bladder cancer tissues and cells was examined by qRT-PCR. Correlation between lnc00518 expression with clinicopathologic characteristics and prognosis of bladder cancer patients was analyzed. In vitro effects of lnc00518 on the cellular behaviors of bladder cancer cells were explored. Moreover, in vivo effect of lnc00518 was evaluated by subcutaneous tumorigenesis in nude mice. The possible miRNA targets of lnc00518 were predicted by bioinformatics and further confirmed by dual-luciferase reporter gene assay, RIP and rescue experiments. Lnc00518 was highly expressed in bladder cancer tissues and cells. Lnc00518 expression was correlated with TNM staging and histological grade of bladder cancer. Besides, the overall survival was lower in bladder cancer patients with high expression of lnc00518 relative to those with low expression. Overexpression of lnc00518 enhanced proliferative, invasive, migratory potentials and clonality, but shortened G0/G1 phase of bladder cancer cells. Lnc00518 knockdown obtained the opposite trends. In vivo experiments revealed that lnc00518 knockdown inhibited subcutaneous tumorigenesis in nude mice. QRT-PCR results indicated that lnc00518 expression was negatively correlated with miRNA-101 expression in bladder cancer cells. Through dual-luciferase reporter gene assay and RIP, we confirmed the binding between lnc00518 and miRNA-101. Furthermore, EZH2 was verified to be the target of miRNA-101. MiRNA-101 knockdown reversed the inhibitory roles of lnc00518 knockdown in proliferative, migratory and invasive potentials of bladder cancer cells. Lnc00518 is highly expressed in bladder cancer and can be served as a predictor of poor prognosis. Lnc00518 promotes the proliferative, invasive and migratory potentials of bladder cancer by upregulating EZH2 via competitively binding to miRNA-101.

Project description:The present study aimed to investigate the potential role of long non-coding RNA growth arrest-specific transcript 5 (lncRNA GAS5) in the progression of esophageal squamous cell carcinoma (ESCC) and to reveal its possible regulatory mechanism. The expression of lncRNA GAS5 in ESCC tissues and cell lines was analyzed using reverse transcription-quantitative polymerase chain reaction and western blot analysis. The overexpression vector pc-GAS5 and control vector pc-negative control (NC), containing no GAS5 sequence, were transfected into ESCC cells. The effects of lncRNA GAS5 overexpression on cell proliferation, cell cycle distribution, cell migration and invasion were then analyzed. Besides, the expression levels of ATM-CHK2 pathway-associated proteins and epithelial-mesenchymal transition (EMT)-associated proteins were measured. Expression of lncRNA GAS5 was downregulated in the ESCC tissues compared with adjacent normal tissues, and was also downregulated in ESCC Kyse450 cells compared with the human esophageal epithelial HET-1A cell line. Additionally, lncRNA GAS5 was successfully overexpressed in ESCC cells following transfection with pc-GAS5. Overexpression of lncRNA GAS5 significantly inhibited cell proliferation, induced cell cycle arrest at G2/M phase and suppressed cellular migration and invasion. When cells were transfected with pc-GAS5, the levels of phosphorylated (p)-ATM serine/threonine protein kinase, p-checkpoint kinase 2 (CHK2), p-cell division cycle 25C, p-cyclin-dependent kinase 1, N-cadherin, vimentin and Snail were significantly increased, whereas that of E-cadherin were markedly decreased. The results of the present study indicate that overexpression of lncRNA GAS5 may inhibit cell proliferation, migration and invasion in ESCC. lncRNA GAS5 overexpression may induce cell cycle arrest at G2/M stage by activating the ATM-CHK2 pathway. The results of the current study further indicate that lncRNA GAS5 overexpression may suppress cell migration and invasion via EMT-associated proteins. lncRNA GAS5 could therefore serve as a potential target for ESCC therapy.

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Dataset Information

Downregulation of GAS5 promotes bladder cancer cell proliferation, partly by regulating CDK6.

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Conclusions

Publications

Downregulation of GAS5 promotes bladder cancer cell proliferation, partly by regulating CDK6.

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