Abstract
BackgroundLong non-coding RNA is essential for the metastasis, invasion, angiogenesis and progression of hepatocellular carcinoma (HCC). However, their specific mechanisms are still controversial. Here, we found that Lnc-MYLK-AS1 is a potential oncogene. We systematically analyzed the clinical significance and mechanism of Lnc-MYLK-AS1 in HCC metastasis, invasion and angiogenesis.MethodsDetermine research goals through bioinformatics analysis. The expression of MYLK-AS1 in matched tumor and non-tumor tissues of 156 HCC patients was detected by quantitative reverse transcription PCR. The in vitro and in vivo biological functions of MYLK-AS1 were examined through the loss of function and function gain experiments. The use of dual luciferase reporter gene analysis, quantitative PCR, Western blotting, and fluorescence in situ hybridization (FISH) clarified the underlying mechanism of this competitive endogenous RNA (ceRNA). ResultsMYLK-AS1 is up-regulated in HCC cell lines and tumor tissues, which is related to tumor progression and enhancement of angiogenesis. Overexpression of MYLK-AS1 promotes the proliferation, metastasis, invasion, and angiogenesis of HCC cells, while down-regulation of MYLK-AS1 can reverse these effects in vivo and in vitro. Dual analysis of luciferase and RNA immunoprecipitation showed that microRNA miR-424-5p is the direct target of MYLK-AS1, and MYLK-AS1 acts as ceRNA, which can regulate angiogenesis in HCC. Mechanism studies have shown that miR-424-5p specifically targets E2F transcription factor 7 (E2F7), while the complex MYLK-AS1/miR-424-5p activates VEGFR2 signaling through E2F7, thereby promoting tumor proliferation and angiogenesis.ConclusionThe up-regulation of MYLK-AS1 is related to tumor cell proliferation, increased angiogenesis and poor prognosis in HCC patients. MYLK-AS1 regulates E2F7 expression and VEGFR2 signaling by acting as a ceRNA of miR-424-5p.