Depleting circ_0088364 restrained cell growth and motility of human hepatocellular carcinoma via circ_0088364-miR-1270-COL4A1 ceRNA pathway

Circular RNA hsa_circ_0088364 (circ_0088364) is a contributory factor in the malignancy of hepatocellular carcinoma (HCC). We aimed to elaborate its role and competing endogenous RNA (ceRNA) mechanism in HCC cell growth and motility. Expression of circ_0088364, microRNA (miR)-1270 and Collagen type IV alpha 1 chain (COL4A1) was measured by real-time quantitative PCR and Western blotting, and their relationships were determined by dual-luciferase reporter assay, RNA immunoprecipitation, biotinylated RNA pull-down, and Spearman's rank correlation analysis. Cellular programs were measured by cell counting kit-8 assay, flow cytometry and transwell assays, Western blotting, and xenograft experiment. Expression of circ_0088364 and COL4A1 was upregulated, and miR-1270 was downregulated in HCC patients' tumors; moreover, there were linear correlations among circ_0088364, miR-1270, and COL4A1 expression. Essentially, circ_0088364 and COL4A1 were ceRNAs for miR-1270 via target binding. In function, silencing circ_0088364 or upregulating miR-1270 could suppress cell proliferation, cell cycle entrance, transwell migration and invasion in Huh7 and HCCLM3 cells, as well as promote apoptosis rate. Moreover, above-mentioned effects were accompanied with reduced B-cell lymphoma (Bcl)-2, N-cadherin and Vimentin levels, and elevated Bcl-2-associated X protein (Bax) and E-cadherin levels. Contrarily, exhausting miR-1270 and restoring COL4A1 could severally abrogate the tumor-suppressive roles of circ_0088364 knockdown and miR-1270 overexpression in HCC cells in vitro. In vivo, silencing circ_0088364 retarded xenograft tumor growth in nude mice induced by Huh7 cells by upregulating miR-1270 and downregulating COL4A1. Blocking circ_0088364 suppressed HCC by inhibiting cell growth and motility via targeting miR-1270-COL4A1 axis.