Long noncoding RNA MIR31HG inhibits hepatocellular carcinoma proliferation and metastasis by sponging microRNA-575 to modulate ST7L expression

Abstract

BackgroundEmerging evidences have indicated that long noncoding RNAs (lncRNAs) play essential roles in the development and progression of cancers. Dysregulation of lncRNA MIR31HG has recently been reported in several types of cancers, and researches on the function of MIR31HG in cancers suggested that MIR31HG could act as either oncogene or tumor suppressor. But the functional involvement of MIR31HG has not been studied in hepatocellular carcinoma (HCC).MethodsIn this study, MTS assays, colony formation assay, Wound-healing assay, Transwell assy, and tumor xenografts experiments were used to identify biological effects of MIR31HG on HCC cells HCC proliferation and metastasis in vitro and in vivo. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were performed to show the interactions of MIR31HG and miR-575. The bioinformatics methods were completed to find the target genes of miR-575. And Dual-luciferase reporter assay and Western blot analysis were further used to confirm the target gene of miR-575.ResultsWe found that overexpression of MIR31HG obviously suppressed HCC proliferation and metastasis in vitro and in vivo, whereas knockdown of MIR31HG had the opposite effects. Besides, overexpression of MIR31HG significantly decreased the expression of microRNA-575 (miR-575), which plays an oncogenic role in HCC. Moreover, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay revealed that MIR31HG exerted tumor-suppressive functions by binding directly to miR-575, and there was a reciprocal inhibition between MIR31HG and miR-575 in the same RNA-induced silencing complex (RISC). Furthermore, overexpression of MIR31HG enhanced the expression of suppression of tumorigenicity 7 like (ST7L), which was identified as a downstream target gene of miR-575. Thus, MIR31HG positively regulated ST7L expression through sponging miR-575, and acted as tumor suppressor in HCC.ConclusionsOverall, our study illuminates the role of MIR31HG as a miRNA sponge in HCC, and sheds new light on lncRNA-directed diagnostics and therapeutics in HCC.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0853-9) contains supplementary material, which is available to authorized users.

LncRNA CACNA1G‐AS1 facilitates hepatocellular carcinoma progression through the miR‐2392/C1orf61 pathway

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Long noncoding MAGI2‐AS3 promotes colorectal cancer progression through regulating miR‐3163/TMEM106B axis

“…In a general way, lncRNA functions as a competitive endogenous RNA by binding with microRNAs (miRNAs) to modulate messenger RNA (mRNA) expression in cancers (Qi et al, 2015). For instance, SNHG8 promotes the progression of endometrial via miR-152/c-MET axis (Yan et al, 2018). lncRNA SNHG14 drives the development of cervical cancer by sponging miR-206 and targeting YWHAZ (Ji, Wang, Bao, Yan, & Ji, 2019).…”

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