Circ_0007429 promotes hepatocellular carcinoma resistance to sorafenib through the miR-377-3p/THBS1 axis.

Abstract

Objective: To elucidate the function of circ_0007429 in hepatocellular carcinoma (HCC) chemoresistance, with a focus on its regulatory mechanisms via the miR-377-3p/THBS1 (Thrombospondin 1) axis.

Methods: The expression levels of circ_0007429, miR-377-3p, and THBS1 mRNA were quantified using quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR). Cell viability was assessed with the CCK-8 assay, and THBS1 protein expression was evaluated by western blotting. The interactions between miR-377-3p and circ_0007429 or THBS1 were confirmed using luciferase reporter assays.

Results: Circ_0007429 expression was substantially upregulated in sorafenib-resistant (SR) HCC cells. Knockdown of circ_0007429 accelerated sorafenib sensitivity by suppressing cell survival. Mechanistically, circ_0007429 acted as a molecular sponge for miR-377-3p, whose activity was increased upon circ_0007429 silencing. THBS1 was recognized as a downstream target of miR-377-3p, and its expression was suppressed by miR-377-3p. Circ_0007429 is a ceRNA for miR-377-3p, thus controlling THBS1 translation and contributing to sorafenib resistance.

Conclusion: Circ_0007429 silencing enhances sorafenib sensitivity in HCC through the miR-377-3p/THBS1 axis. circ_0007429 may be a biomarker and therapeutic target for overcoming chemoresistance in HCC.