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Lopinavir enhances anoikis by remodeling autophagy in a circRNA-dependent manner.
Wu, Yaran; Chen, Yang; Yan, Xiaojing; Dai, Xufang; Liao, Yaling; Yuan, Jing; Wang, Liting; Liu, Dong; Niu, Dun; Sun, Liangbo; Chen, Lingxi; Zhang, Yang; Xiang, Li; Chen, An; Li, Shuhui; Xiang, Wei; Ni, Zhenhong; Chen, Ming; He, Fengtian; Yang, Mingzhen; Lian, Jiqin.
Affiliation
  • Wu Y; Department of Clinical Laboratory Medicine, Southwest Hospital, Army Medical University, Chongqing, China.
  • Chen Y; Department of Clinical Biochemistry, Faculty of Pharmacy and Laboratory Medicine, Army Medical University, Chongqing, China.
  • Yan X; Department of Clinical Biochemistry, Faculty of Pharmacy and Laboratory Medicine, Army Medical University, Chongqing, China.
  • Dai X; Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China.
  • Liao Y; Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Army Medical University, Chongqing, China.
  • Yuan J; College of Education and Science, Chongqing Normal University, Chongqing, China.
  • Wang L; Department of Clinical Biochemistry, Faculty of Pharmacy and Laboratory Medicine, Army Medical University, Chongqing, China.
  • Liu D; Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Army Medical University, Chongqing, China.
  • Niu D; Biomedical Analysis Center, Army Medical University, Chongqing, China.
  • Sun L; Department of Clinical Biochemistry, Faculty of Pharmacy and Laboratory Medicine, Army Medical University, Chongqing, China.
  • Chen L; Department of Clinical Biochemistry, Faculty of Pharmacy and Laboratory Medicine, Army Medical University, Chongqing, China.
  • Zhang Y; Department of Clinical Biochemistry, Faculty of Pharmacy and Laboratory Medicine, Army Medical University, Chongqing, China.
  • Xiang L; Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Army Medical University, Chongqing, China.
  • Chen A; Department of Clinical Biochemistry, Faculty of Pharmacy and Laboratory Medicine, Army Medical University, Chongqing, China.
  • Li S; Department of Clinical Biochemistry, Faculty of Pharmacy and Laboratory Medicine, Army Medical University, Chongqing, China.
  • Xiang W; Department of Clinical Biochemistry, Faculty of Pharmacy and Laboratory Medicine, Army Medical University, Chongqing, China.
  • Ni Z; Department of Clinical Biochemistry, Faculty of Pharmacy and Laboratory Medicine, Army Medical University, Chongqing, China.
  • Chen M; State Key Laboratory of Trauma, Burns and Combined Injury, Department of Rehabilitation Medicine, Daping Hospital, Army Medical University, Chongqing, China.
  • He F; State Key Laboratory of Trauma, Burns and Combined Injury, Department of Rehabilitation Medicine, Daping Hospital, Army Medical University, Chongqing, China.
  • Yang M; Department of Clinical Laboratory Medicine, Southwest Hospital, Army Medical University, Chongqing, China.
  • Lian J; Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Army Medical University, Chongqing, China.
Autophagy ; 20(7): 1651-1672, 2024 07.
Article in En | MEDLINE | ID: mdl-38433354
ABSTRACT
Macroautophagy/autophagy-mediated anoikis resistance is crucial for tumor metastasis. As a key autophagy-related protein, ATG4B has been demonstrated to be a prospective anti-tumor target. However, the existing ATG4B inhibitors are still far from clinical application, especially for tumor metastasis. 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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autophagy / Cysteine Endopeptidases / Anoikis / Lopinavir / RNA, Circular Limits: Animals / Humans Language: En Journal: Autophagy Year: 2024 Document type: Article Affiliation country: China Country of publication: Estados Unidos

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autophagy / Cysteine Endopeptidases / Anoikis / Lopinavir / RNA, Circular Limits: Animals / Humans Language: En Journal: Autophagy Year: 2024 Document type: Article Affiliation country: China Country of publication: Estados Unidos