Abstract
BackgroundIncreasing evidence has demonstrated that long noncoding RNAs (lncRNAs) have regulatory functions in hepatocellular carcinoma (HCC). The link between lincSCRG1 and HCC remains unclear.MethodsTo explore the lincSCRG1 regulation axis, bioinformatics, RIP and luciferase reporter assay were performed. The expressions of lincSCRG1-miR26a-SKP2 were detected in HCC tissues and cell lines through qPCR and western blot. The functions of HCC cells were investigated through in vitro assays (MTT, colony formation, transwell and flow cytometry) and the inner effect of lincSCRG1-miR26a in vivo was evaluated by xenografts and liver metatstatic nude mice models.ResultsLincSCRG1 was found to be strongly elevated in human HCC tissues and cell lines. MiR26a and S phase kinase-related protein 2 (SKP2) were predicted as the target miRNA for lincSCRG1 and the target gene for miR26a with direct binding sites, respectively. LincSCRG1 was verified as a competing endogenous RNA (ceRNA) via negative regulation of miR26a and derepression of SKP2 in HCC cells. Both overexpression of lincSCRG1 (ov-lincSCRG1) and inhibition of miR26a (in-miR26a) obviously stimulated cellular viability, colony formation, migration and proliferation of S phase cells and also significantly increased the protein levels of cyclinD1, CDK4, MMP2/3/9, Vimentin, and N-cadherin or inhibited the protein level of E-cadherin of HCC cells, while knockdown of lincSCRG1 (sh-lincSCRG1) and upregulation of miR26a (mi-miR26a) had the opposite effects on HCC cells. Cotransfection of in-miR26a or overexpression of SKP2 (ov-SKP2) with sh-lincSCRG1 could rescue the anticancer functions of sh-lincSCRG1, including suppressing proliferation and migration of HCC cells. Additionally, sh-lincSCRG1 could effectively inhibit the growth of subcutaneous xenograft tumours and lung metastasis, while the anticancer effect of sh-lincSCRG1 could be reversed by cotransfection of in-miR26a.ConclusionsLincSCRG1 acts as a ceRNA of miR26a to restrict its ability to derepress SKP2, thereby inducing the proliferation and migration of HCC cells in vitro and in vivo. Depletion of lincSCRG1 could be used as a potential therapeutic approach in HCC.
Highlights
Increasing evidence has demonstrated that long noncoding RNAs have regulatory functions in hepatocellular carcinoma (HCC)
The expression of lincSCRG1 was substantially upregulated in both human liver tissues and HCC cell lines To explore the role of HCC-related long noncoding RNAs (lncRNAs), we focused on lincSCRG1 (XLOC_004166; lnc-Hand2–2:1; located on chr4:173453013–173,520,960; transcript length 3118 bp)
PCR analysis indicated that lincSCRG1expression was clearly elevated in the human HCC tissues compared to the adjacent liver tissues
Summary
Increasing evidence has demonstrated that long noncoding RNAs (lncRNAs) have regulatory functions in hepatocellular carcinoma (HCC). The link between lincSCRG1 and HCC remains unclear. Hepatocellular carcinoma (HCC) is regarded as the most common primary malignancy of the liver and a major cause of mortality [1]. In view of its malignancy and the fact that its pathogenesis is still a mystery, it is necessary to elucidate the essential pathogenesis of HCC for the identification of novel therapeutic targets. The exact biotic mechanisms and functions of most lncRNAs in HCC remain largely unknown. Nearly 30 deregulated lncRNAs have been identifiedas being associated with HCC [4]. LncRNAs affect cell proliferation, apoptosis and metastasis and regulatethe tumour microenvironment in HCC, eventually causing tumour development [5]
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