Lopinavir enhances anoikis by remodeling autophagy in a circRNA-dependent manner

In this study, we identified a novel circRNA, circSPECC1, that interacted with ATG4B. CircSPECC1 facilitated liquid-liquid phase separation of ATG4B, which boosted the ubiquitination and degradation of ATG4B in gastric cancer (GC) cells. Thus, pharmacological addition of circSPECC1 May serve as an innovative approach to suppress autophagy by targeting ATG4B. Specifically, the circSPECC1 underwent significant m6A modification in GC cells and was subsequently recognized and suppressed by the m6A reader protein ELAVL1/HuR. The activation of the ELAVL1-circSPECC1-ATG4B pathway was demonstrated to mediate anoikis resistance in GC cells. Moreover, we also verified that the above pathway was closely related to metastasis in tissues from GC patients. Furthermore, we determined that the FDA-approved compound lopinavir efficiently enhanced anoikis and prevented metastasis by eliminating repression of ELAVL1 on circSPECC1. In summary, this study provides novel insights into ATG4B-mediated autophagy and introduces a viable clinical inhibitor of autophagy, which may be beneficial for the treatment of GC with metastasis.PMID:38433354 | DOI:10.1080/15548627.2024.2325304

Source: Autophagy - March 4, 2024 Category: Cytology Authors: Yaran Wu Yang Chen Xiaojing Yan Xufang Dai Yaling Liao Jing Yuan Liting Wang Dong Liu Dun Niu Liangbo Sun Lingxi Chen Yang Zhang Li Xiang An Chen Shuhui Li Wei Xiang Zhenhong Ni Ming Chen Fengtian He Mingzhen Yang Jiqin Lian Source Type: research