CircRNA-001241 mediates sorafenib resistance of hepatocellular carcinoma cells by sponging miR-21-5p and regulating TIMP3 expression.

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the major malignancies worldwide and its incidence is on the rise, closely related to advanced liver disease. Sorafenib chemotherapy is one of the main treatment options for patients with advanced HCC. Despite several reports on HCC multidrug resistance, the underlying regulatory mechanisms are still unclear. In this study, we found circ-001241 was significantly upregulated in HCC tissues and cells. Knockdown of circ-001241 markedly inhibited HCC cell proliferation and decreased sorafenib-resistance. More importantly, circRNA acts as a ceRNA to suppress the expression and activity of miR-21-5p, leading to the increase in TIMP3 expression. In addition, circRNA-001241 facilitated HCC sorafenib-resistance by regulating the miR-21-5p/TIMP3 axis. Taken together, our study elucidated the oncogenic role of circ-001241 in mediating sorafenib resistance in HCC, providing insights and opportunities to overcome sorafenib resistance in patients with advanced hepatocellular carcinoma.