Chen Lingxi, Sun Liangbo, Dai Xufang, Li Tao, Yan Xiaojing, Zhang Yueting, Xiao Hanxi, Shen Xiaodong, Huang Gang, Xiang Wei, Zhang Yan, Tan Dehong, Yang Shiming, Nie Yongzhan, Huang Xuequan, Lian Jiqin, He Fengtian
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.
Front Cell Dev Biol. 2021 Aug 2;9:687524. doi: 10.3389/fcell.2021.687524. eCollection 2021.
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 and . 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.
自噬与癌细胞的生长和耐药性密切相关，自噬相关蛋白4B（ATG4B）在自噬过程中发挥关键作用。长链非编码RNA（lncRNA）结直肠癌差异表达基因（CRNDE）促进肝细胞癌（HCC）的进展，但CRNDE的促肿瘤作用是否与ATG4B和自噬的调节相关尚不清楚。在此，我们首次证明CRNDE通过上调HCC细胞中的ATG4B触发自噬。机制上，CRNDE通过隔离miR-543增强ATG4B mRNA的稳定性，导致HCC细胞中ATG4B和自噬水平升高。此外，索拉非尼诱导HCC细胞中CRNDE、ATG4B以及自噬。敲低CRNDE使HCC细胞对索拉非尼敏感。总之，这些结果表明CRNDE驱动ATG4B介导的自噬，这减弱了HCC细胞对索拉非尼的敏感性，提示CRNDE/ATG4B/自噬通路可能是开发HCC治疗中索拉非尼增敏措施的新靶点。
