Hsa-miR-4277 Decelerates the Metabolism or Clearance of Sorafenib in HCC Cells and Enhances the Sensitivity of HCC Cells to Sorafenib by Targeting cyp3a4

Frontiers in Oncology

Boan Li²  Xi He³  Shaojie Xin³  Bing Zhu³  Shaoli You³  Junfeng Hao⁴  Xiaojuan Li⁵  Zhijie Wang⁵  Huiwei Sun⁵  Qiyu Jiang⁵  Yantao Chai⁵ 

[1] Chinese People’s Liberation Army (PLA) Medical School, Beijing, China;Department of Clinical Laboratory, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China;Department of Liver Disease of Chinese PLA General Hospital, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China;Department of Nephrology, Jin Qiu Hospital of Liaoning Province/Geriatric Hospital of Liaoning Province, Shenyang, China;Institute of Infectious Disease, Department of Infectious Disease, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China;

关键词: advanced hepatocellular carcinoma;    cytochrome P450 3A4;    miR-4277;    chemoresistance;    sorafenib;    metabolism or clearance;   

DOI  :  10.3389/fonc.2021.735447

来源: DOAJ

【 摘 要 】

Increasing evidence has shown that the metabolism and clearance of molecular targeted agents, such as sorafenib, plays an important role in mediating the resistance of HCC cells to these agents. Metabolism of sorafenib is performed by oxidative metabolism, which is initially mediated by CYP3A4. Thus, targeting CYP3A4 is a promising approach to enhance the sensitivity of HCC cells to chemotherapeutic agents. In the present work, we examined the association between CYP3A4 and the prognosis of HCC patients receiving sorafenib. Using the online tool miRDB, we predicted that has-microRNA-4277 (miR-4277), an online miRNA targets the 3’UTR of the transcript of cyp3a4. Furthermore, overexpression of miR-4277 in HCC cells repressed the expression of CYP3A4 and reduced the elimination of sorafenib in HCC cells. Moreover, miR-4277 enhanced the sensitivity of HCC cells to sorafenib in vitro and in vivo. Therefore, our results not only expand our understanding of CYP3A4 regulation in HCC, but also provide evidence for the use of miR-4277 as a potential therapeutic in advanced HCC.

【 授权许可】

Unknown