LncRNA CRNDE Promotes ATG4B-Mediated Autophagy and Alleviates the Sensitivity of Sorafenib in Hepatocellular Carcinoma Cells

Frontiers in Cell and Developmental Biology

Xuequan Huang¹  Xufang Dai²  Hanxi Xiao³  Xiaojing Yan³  Xiaodong Shen³  Lingxi Chen³  Gang Huang³  Wei Xiang³  Fengtian He³  Yueting Zhang³  Tao Li³  Yan Zhang³  Liangbo Sun⁴  Jiqin Lian⁴  Shiming Yang⁵  Dehong Tan⁶  Yongzhan Nie⁷ 

[1] Center of Minimally Invasive Intervention, Southwest Hospital, Army Medical University, Chongqing, China;College of Educational Science, Chongqing Normal University, Chongqing, China;Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Army Medical University, Chongqing, China;Department of Clinical Biochemistry, Faculty of Pharmacy and Laboratory Medicine, Army Medical University, Chongqing, China;Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China;Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Army Medical University, Chongqing, China;State Key Laboratory of Cancer Biology, Air Force Medical University, Xi’an, China;

关键词: hepatocellular carcinoma;    CRNDE;    ATG4B;    autophagy;    sorafenib;   

DOI  :  10.3389/fcell.2021.687524

来源: DOAJ

【 摘 要 】

Autophagy is closely related to the growth and drug resistance of cancer cells, and autophagy related 4B (ATG4B) performs a crucial role in the process of autophagy. The long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) promotes the progression of hepatocellular carcinoma (HCC), but it is unclear whether the tumor-promoting effect of CRNDE is associated with the regulation of ATG4B and autophagy. Herein, we for the first time demonstrated that CRNDE triggered autophagy via upregulating ATG4B in HCC cells. Mechanistically, CRNDE enhanced the stability of ATG4B mRNA by sequestrating miR-543, leading to the elevation of ATG4B and autophagy in HCC cells. Moreover, sorafenib induced CRNDE and ATG4B as well as autophagy in HCC cells. Knockdown of CRNDE sensitized HCC cells to sorafenib in vitro and in vivo. Collectively, these results reveal that CRNDE drives ATG4B-mediated autophagy, which attenuates the sensitivity of sorafenib in HCC cells, suggesting that the pathway CRNDE/ATG4B/autophagy may be a novel target to develop sensitizing measures of sorafenib in HCC treatment.

【 授权许可】

Unknown