Dataset Information

Long non-coding RNA SNHG5 promotes human hepatocellular carcinoma progression by regulating miR-26a-5p/GSK3? signal pathway.

ABSTRACT: Accumulating evidence have suggested that long non-coding RNAs (lncRNAs) had malfunctioning roles in the development of human cancers. The present study aimed to investigate the role of lncRNA small nucleolar RNA host gene 5 (SNHG5) in hepatocellular carcinoma (HCC) progression using human tissues and cell lines. The quantitative real-time PCR results showed that SNHG5 was up-regulated in both HCC tissues and hepatoma cell lines and was closely associated with tumor size, hepatitis B virus infection, histologic grade, TNM stage, and portal vein tumor thrombus (PVTT) in HCC patients. Knockdown of SNHG5 induced apoptosis and repressed cell cycle progression, cell growth, and metastasis in hepatoma cell lines, whereas overexpression of SNHG5 had the opposite effects. In vivo functional assay, xenograft tumors grown from SNHG5-knockdown cells had smaller mean volumes than the tumors grown from negative control cells. Further investigations showed that SNHG5 may act as a competing endogenous RNA by competitively binding miR-26a-5p and thereby modulating the derepression of downstream target GSK3?, which were further confirmed by luciferase reporter assay. Functionally, SNHG5 promotes tumor growth and metastasis by activating Wnt/?-catenin pathway and inducing epithelial to mesenchymal transition (EMT). Taken together, SNHG5 promotes HCC progression by competitively binding miR-26a-5p and regulating GSK3? and Wnt/?-catenin signal pathway.

SUBMITTER: Li Y

PROVIDER: S-EPMC6117363 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Long non-coding RNA SNHG5 promotes human hepatocellular carcinoma progression by regulating miR-26a-5p/GSK3β signal pathway.

Li Yarui Y Guo Dan D Zhao Yan Y Ren Mudan M Lu Guifang G Wang Yun Y Zhang Juan J Mi Chen C He Shuixiang S Lu Xinlan X

Cell death & disease 20180830 9

Accumulating evidence have suggested that long non-coding RNAs (lncRNAs) had malfunctioning roles in the development of human cancers. The present study aimed to investigate the role of lncRNA small nucleolar RNA host gene 5 (SNHG5) in hepatocellular carcinoma (HCC) progression using human tissues and cell lines. The quantitative real-time PCR results showed that SNHG5 was up-regulated in both HCC tissues and hepatoma cell lines and was closely associated with tumor size, hepatitis B virus infec ...[more]

PMID: 30166525

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Project description:PurposeHepatocellular carcinoma(HCC) is the most common type of liver cancer and the sixth largest common cancer worldwide. Although surgical resection, hepatic arterial chemoembolization, targeted drugs and immunotherapy are currently available, the mortality of advanced patients remains high. Therefore, new therapeutic targets are urgently needed. In recent years, many studies have found that The long non-coding RNA(lncRNA) has multiple functions in human tumors, including participating in epigenetic, transcriptional, post-transcriptional and translational regulation, and is closely related to the progression of HCC. The purpose of this study was to investigate the role of AC006329.1 in HCC progression and provide theoretical guidance for finding new targets.Patients and methodsAC006329.1 was screened out by transcriptome sequencing and quantitative real-time polymerase chain reaction (qRT-PCR). Then a series of functional tests in vivo and in vitro were conducted to investigate the effects of AC006329.1 on HCC progression and metastasis. Epithelial-mesenchymal transformation (EMT) of HCC was detected by Western blot and immunofluorescence staining. The targeted miRNA and downstream gene of AC006329.1 were predicted by databases and the pathway regulation axis eventually validated by dual luciferase reporter assays, qRT-PCR and WB.ResultsAC006329.1 was found high expressed in HCC tissues and cell lines by qRT-PCR. The prognosis of HCC patients with high expressed AC006329.1 was poor. In vitro and in vivo, overexpression of AC006329.1 can promote the progression, metastasis and EMT of HCC by acting as a sponge of miR-127-5p to increase the expression of SHC3. In addition, up-regulation of miR-127-5p or knockdown of SHC3 can both reverse the promoting effects of AC006329.1 on progression, metastasis and EMT of HCC. Finally, WB and qRT-PCR analysis was discovered that AC006329.1 can facilitate HCC progression, EMT and metastasis by competitively inhibiting miR-127-5p to activate SHC3/ERK signaling pathway.ConclusionThese above experimental results confirmed that AC006329.1 can facilitate HCC progression, EMT and metastasis by acting as a competing endogenous RNA (ceRNA) to inhibit miR-127-5p and activate SHC3/ERK signaling pathway.

Dataset Information

Long non-coding RNA SNHG5 promotes human hepatocellular carcinoma progression by regulating miR-26a-5p/GSK3? signal pathway.

Publications

Long non-coding RNA SNHG5 promotes human hepatocellular carcinoma progression by regulating miR-26a-5p/GSK3β signal pathway.

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