Circ_LDLR Knockdown Suppresses Progression of Hepatocellular Carcinoma via Modulating miR-7/RNF38 Axis.

Abstract

BackgroundHepatocellular carcinoma (HCC) is a horrible malignancy derived from liver. Circular RNAs (circRNAs) act important roles in the pathogenesis and progression of human diseases, including HCC. The current assay intended to investigate the function of circRNA low-density lipoprotein receptor (circ_LDLR) in HCC and clarify the underlying mechanism.Materials and MethodsExpression of circ_LDLR, microRNA (miR)-7 and ring finger protein 38 (RNF38) was determined by quantitative real-time PCR (qRT-PCR) or Western blot analysis. Flow cytometry was used to detect cell cycle distribution and apoptosis. Cell colony formation ability and viability were examined by colony formation and methyl thiazolyl tetrazolium (MTT) assays, respectively. Levels of cell proliferation and epithelia-mesenchymal transition (EMT) biomarker proteins were analyzed via Western blot assay. Cell migration and invasion were monitored by Transwell assay, and target relationship between miR-7 and circ_LDLR or RNF38 was validated by dual-luciferase reporter assay. Xenograft model was established to explore the role of circ_LDLR in vivo.ResultsExpression of circ_LDLR and RNF38 was upregulated, but miR-7 expression was downregulated in HCC tissues and cells. Circ_LDLR knockdown significantly inhibited cell proliferation, migration, invasion and EMT in HCC cells. Circ_LDLR acted as a sponge of miR-7, and interference of miR-7 could attenuate circ_LDLR knockdown-induced inhibitory effects on malignant behaviors of HCC cells. Besides, miR-7 also repressed cell proliferation and metastasis of HCC cells, by targeting RNF38. Depletion of circ_LDLR could suppress tumor growth in vivo.ConclusionDepletion of circ_LDLR restrained HCC cell proliferation, metastasis and tumorigenesis through the regulation on miR-7/RNF38 axis, affording a promising therapeutic target for HCC.