CircPHKB decreases the sensitivity of liver cancer cells to sorafenib via miR-1234-3p/CYP2W1 axis

• Published in: Genomics (San Diego, Calif.) Vol. 116; no. 1; p. 110764
• Main Authors: Chen, Lingxi, Xiao, Hanxi, Wu, Yaran, Yan, Dongjing, Shan, Meihua, Sun, Liangbo, Yan, Xiaojing, Liu, Dong, Li, Tao, Zhang, Yang, Xiang, Li, Chen, An, Li, Shuhui, Xiang, Wei, Ni, Zhenhong, He, Fengtian, Yang, Mingzhen, Lian, Jiqin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2024
• Subjects: Carcinoma, Hepatocellular - drug therapy; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - metabolism; Cell Line, Tumor; Cell Proliferation; circPHKB; CYP2W1; Cytochrome P450 Family 2 - genetics; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Liver cancer cells; Liver Neoplasms - drug therapy; Liver Neoplasms - genetics; Liver Neoplasms - metabolism; MicroRNAs - metabolism; miR-1234-3p; Sorafenib; Sorafenib - pharmacology; Sorafenib - therapeutic use; Up-Regulation; CYP2W1; miR-1234-3p; Liver cancer cells; circPHKB; Sorafenib
• ISSN: 0888-7543; 1089-8646; 1089-8646
• DOI: 10.1016/j.ygeno.2023.110764

Sorafenib is currently the first-line treatment for patients with advanced liver cancer, but its therapeutic efficacy declines significantly after a few months of treatment. Therefore, it is of great importance to investigate the regulatory mechanisms of sorafenib sensitivity in liver cancer cells. In this study, we provided initial evidence demonstrating that circPHKB, a novel circRNA markedly overexpressed in sorafenib-treated liver cancer cells, attenuated the sensitivity of liver cancer cells to sorafenib. Mechanically, circPHKB sequestered miR-1234-3p, resulting in the up-regulation of cytochrome P450 family 2 subfamily W member 1 (CYP2W1), thereby reducing the killing effect of sorafenib on liver cancer cells. Moreover, knockdown of circPHKB sensitized liver cancer cells to sorafenib in vivo. The findings reveal a novel circPHKB/miR-1234-3p/CYP2W1 pathway that decreases the sensitivity of liver cancer cells to sorafenib, suggesting that circPHKB and the axis may serve as promising targets to improve the therapeutic efficacy of sorafenib against liver cancer. •The overexpression of circPHKB decreases the sensitivity of liver cancer cells to sorafenib.•Sorafenib activates circPHKB/miR-1234-3p/ CYP2W1 signal axis in liver cancer cells.•Suppression of the circPHKB/miR-1234-3p/ CYP2W1 signal axis enhances the sensitivity of liver cancer cells to sorafenib.