Dataset Information

GAS5 Regulates RECK Expression and Inhibits Invasion Potential of HCC Cells by Sponging miR-135b.

ABSTRACT: Objectives:Long noncoding RNA (LncRNA) growth arrest-specific 5 (GAS5) has been characterized as a tumor suppressor in numerous kinds of human cancers. Its anticancer function in hepatocellular carcinoma (HCC) includes repression of cell proliferation and metastasis, leaving the internal mechanisms unclear. In this study, we intended to examine the anti-invasion effects of GAS5 on HCC and explore the downstream regulatory mechanisms. Methods:Expression of GAS5 and microRNA-135b (miR-135b) was analyzed by qRT-PCR in paired HCC tissue samples. Their correlation with HCC patients' survival was determined. Transwell assays were done to evaluate in vitro invasion ability. Targeting of GAS5 and RECK by miR-135b was confirmed by qRT-PCR, western blot, and luciferase reporter assays. Results:Decreased GAS5 and increased miR-135b in HCC inversely correlate with each other and both correlate with poor prognosis of HCC patients. Functionally, GAS5 suppresses while miR-135b promotes HCC cell invasion capacities in vitro. Mechanistically, GAS5 is a target of miR-135b. Furthermore, GAS5 positively regulates expression of RECK, also a target of miR-135b, which further inhibits MMP-2 expression and contributes to invasion repression. Conclusion:GAS5 acted as a tumor suppressor in HCC invasion in a competing endogenous RNA manner. Our findings indicate that GAS5 is a promising therapeutic target for HCC treatment.

SUBMITTER: Yang L

PROVIDER: S-EPMC6348854 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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GAS5 Regulates RECK Expression and Inhibits Invasion Potential of HCC Cells by Sponging miR-135b.

Yang Liang L Jiang Jianshuai J

BioMed research international 20190113

<h4>Objectives</h4>Long noncoding RNA (LncRNA) growth arrest-specific 5 (GAS5) has been characterized as a tumor suppressor in numerous kinds of human cancers. Its anticancer function in hepatocellular carcinoma (HCC) includes repression of cell proliferation and metastasis, leaving the internal mechanisms unclear. In this study, we intended to examine the anti-invasion effects of GAS5 on HCC and explore the downstream regulatory mechanisms.<h4>Methods</h4>Expression of GAS5 and microRNA-135b (m ...[more]

PMID: 30733959

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Project description:ObjectivesThis research aims to verify that the long non-coding RNA differentiation antagonizing nonprotein coding RNA (LncRNA DANCR) could modulate the proliferation and metastasis of hepatocellular carcinoma (HCC), and it thus may work as a novel biomarker to render new orientation for early diagnosis and clinical therapy of HCC.Materials and methodsFirstly, qRT-PCR was used to detect the expression of genes including LncRNA DANCR and miR-27a-3p. Next, MTT assay, Ethynyldeoxyuridine (EdU) analysis and clone formation assay were used for investigating cell growth and proliferation. Meanwhile, transwell assay and wound healing assay were applied to evaluate the capacity of cell metastasis and motility, respectively. In addition, bioinformatic analysis and dual-luciferase reporter assay were applied to analyse molecular interaction. Next, we conducted immunofluorescence and Western blot for mechanic investigation. Last but not the least, xenograft tumours in nude mice were built by subcutaneously injecting Hep3B cells stably transfected with sh-NC and sh-DANCR to detect proliferation and SMMC-7721 cells stably transfected with sh-NC and sh-DANCR to investigate metastasis.ResultsThe results of qRT-PCR and bioinformatic analysis revealed the high expression of DANCR in HCC. DANCR accelerated proliferation and metastasis of HCC cells and the knockdown of DANCR had the opposite effect. Meanwhile, xenograft tumours in sh-DANCR group grow slower and have smaller volumes compared with negative control group. Next, the antineoplastic effect of miR-27a-3p on cell growth and motility of HCC was confirmed. In addition, we clarified that DANCR acted as a ceRNA to decoy miR-27a-3p via mediating ROCK1/LIMK1/COFILIN1 pathway. In the end, we validated that DANCR/miR-27a-3p axis regulates EMT progression by cell immunofluorescence and Western blot.ConclusionsIn a word, DANCR promotes HCC development and induces EMT by decoying miR-27a-3p to regulate ROCK1/LIMK1/COFILIN1 pathway.

Project description:Long non‑coding RNAs (lncRNAs) have been revealed to have a marked effect in cardiovascular diseases, including during cardiac development, cardiac hypertrophy, myocardial fibrosis and myocardial ischemic injury. The mechanism of myocardial ischemia‑reperfusion injury (MIRI) is very complicated. Although studies have confirmed that lncRNAs are involved, the specific mechanism remains largely unknown. The lncRNA growth arrest specific 5 (GAS5) is known as a regulator of a number of diseases, including certain cancer types. The present study aimed to investigate the function of lncRNA GAS5 in MIRI. The present study reported that the expression of lncRNA GAS5 in H9c2 cells treated with anoxia and reoxygenation was significantly upregulated compared with the control group (P<0.05). Similarly, the expression of lncRNA GAS5 in myocardial tissue obtained from rats treated with MIRI was significantly upregulated compared with the untreated controls (P<0.05). Silencing of lncRNA GAS5 was able to attenuate myocardial damage, as cell viability increased and the apoptosis rate decreased. Classical apoptotic proteins involved in MIRI, including B‑cell lymphoma 2, Bcl‑2‑associated X protein and cleaved caspase‑3, also exhibited the same trend. At the same time, when lncRNA GAS5 was silenced, microRNA (miR)‑532‑5p, which was originally expressed at the stage of injury, was upregulated. The luciferase reporter assay results indicated that the lncRNA GAS5 functioned as a molecular sponge of miR‑532‑5p. The gain‑ and loss‑of‑function analysis of miR‑532‑5p indicated that it was involved in the regulation of MIRI; the trend of results following its overexpression was also consistent with the trend observed following the silencing of lncRNA GAS5. Notably, the protective effect of lncRNA GAS5 silencing on cells was attenuated by miR‑532‑5p inhibition. Phosphatase and tensin homolog was revealed to be a key target gene for the function of lncRNA GAS5, and its regulation was achieved via binding to miR‑532‑5p. In other words, silencing lncRNA GAS5 ultimately promoted the activation of the phosphoinositide‑3‑kinase (PI3K)/protein kinase B pathway (AKT) to reduce myocardial damage. Therefore, lncRNA GAS5 was able to regulate MIRI through the PI3K/AKT apoptosis pathway by sponging miR‑532‑5p.

Dataset Information

GAS5 Regulates RECK Expression and Inhibits Invasion Potential of HCC Cells by Sponging miR-135b.

Publications

GAS5 Regulates RECK Expression and Inhibits Invasion Potential of HCC Cells by Sponging miR-135b.

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