Inhibition of CYP1B1 by miR-200b-3p increases the sensitivity of paclitaxel in hepatocellular carcinoma treatment

Abstract

Liver cancer ranks as the third leading cause of cancer-related death worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90 % of primary liver cancer cases. Elevated expression of drug-metabolizing enzyme CYP1B1 in HCC has been identified as a potential contributor to primary paclitaxel (PTX) resistance. This study demonstrated that miR-200b-3p suppresses CYP1B1 expression in HCC cells. Meanwhile, miR-200b-3p was significantly downregulated in HCC tissues compared to adjacent normal tissues and negatively correlated with CYP1B1 expression. In addition, miR-200b-3p sensitized HCC to PTX in vitro and in vivo patient-derived xenograft (PDX) models by inhibiting CYP1B1, promoting PTX-induced microtubule polymerization, and enhancing its cell cycle-blocking effects. These findings indicate that miR-200b-3p could serve as a promising therapeutic strategy by directly targeting CYP1B1 in HCC.