Down-regulated HSA_circ_0003528 inhibits hepatocellular carcinoma aggressiveness via the miR-212-3p/XIAP axis

Hepatocellular carcinoma (HCC) is characterized by a high mortality rate. Dysregulated circular RNAs (circRNAs) play a vital role in HCC. We aimed to study the role of circ_0003528 in HCC and its fundamental molecular mechanisms. HSA_circ_0003528 was identified through bioinformatics dataset analysis. The binding sites between mRNA and miRNA were predicted using online bioinformatics tools. The interaction between miR-212-3p and X-linked inhibitor of apoptosis protein (XIAP) or circ_0003528 was confirmed through the luciferase reporter assay. RT-qPCR and western blot assays were used to analyze the expression of all miRNAs/mRNAs and proteins. Cellular functions were evaluated using the MTT and TUNEL assays. A xenograft model was established to evaluate the function of circ_0003528 in vivo. Circ_0003528 was dramatically overexpressed in HepG2 and HUH7 cells. However, knockdown of circ_0003528 suppressed the aggressiveness of HCC cells and tumor growth both in vitro and in vivo. Furthermore, binding of miR-212-3p to circ_0003528 and XIAP was verified. Downregulation of miR-212-3p abrogated the effects of si-circ_0003528 on cell viability and apoptosis, and upregulation of XIAP antagonized the functions of the miR-212-3p mimic in HCC cells. circ_0003528 contributes to the development of HCC in vitro and in vivo via the miR-212-3p/XIAP axis. Hence, circ_0003528 knockdown may be a potential therapeutic strategy for HCC treatment.

Automated summary

circ_0003528 is overexpressed in hepatocellular carcinoma (HCC) and knockdown of circ_0003528 suppresses tumor aggressiveness and growth. miR-212-3p functions through interaction with circ_0003528 and XIAP. Knockdown of circ_0003528 may be a potential therapeutic strategy for HCC treatment.