PMID- 35697078 OWN - NLM STAT- MEDLINE DCOM- 20220719 LR - 20221005 IS - 1090-2422 (Electronic) IS - 0014-4827 (Linking) VI - 418 IP - 1 DP - 2022 Sep 1 TI - PLIN2 promotes HCC cells proliferation by inhibiting the degradation of HIF1alpha. PG - 113244 LID - S0014-4827(22)00237-3 [pii] LID - 10.1016/j.yexcr.2022.113244 [doi] AB - PLIN2 has been found to be dysregulated in several human malignancies, which influences cancer progression. However, the roles of PLIN2 in regulating hepatocellular carcinoma (HCC) progression are still unclear. Here, we revealed that PLIN2 was frequently upregulated in HCC cells and tissues, and increased PLIN2 expression was associated with poor prognosis outcomes in HCC. In HCC cells, overexpressing PLIN2 promoted cell proliferation, PLIN2-deficiency inhibited cell vitality. Mechanistically, silencing of PLIN2 expression downregulated hypoxia inducible factor 1-alpha (HIF1alpha) expression and this downregulation in turn inhibited the targeting genes of HIF1alpha. Furthermore, we found that PLIN2 stabilized and retarded the degradation of the HIF1alpha through autophagy-lysosomal pathway by inhibiting AMPK/ULK1. Collectively, we clarified the carcinogenic role of PLIN2 in HCC and suggested a prognostic biomarker for diagnosis and clinical therapy in the future. CI - Copyright (c) 2022 Elsevier Inc. All rights reserved. FAU - Liu, Wuguang AU - Liu W AD - Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian, 116027, China; CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China. FAU - Liu, Xiaolong AU - Liu X AD - CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China. FAU - Liu, Ying AU - Liu Y AD - Department of Oncology, The Affiliated Zhongshan Hospital of Dalian University, Dalian, 116027, China. FAU - Ling, Ting AU - Ling T AD - CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China. FAU - Chen, Di AU - Chen D AD - CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China. FAU - Otkur, Wuxiyar AU - Otkur W AD - CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China. FAU - Zhao, Hailong AU - Zhao H AD - Department of General Surgery, People's Hospital of Huangyuan County, Huangyuan County, Xining, 812100, China. FAU - Ma, Ming AU - Ma M AD - Department of General Surgery, People's Hospital of Huangyuan County, Huangyuan County, Xining, 812100, China. FAU - Ma, Kexin AU - Ma K AD - Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian, 116027, China. FAU - Dong, Bing AU - Dong B AD - Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian, 116027, China. FAU - Yang, Zexuan AU - Yang Z AD - Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian, 116027, China. FAU - Piao, Hai-Long AU - Piao HL AD - CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China. Electronic address: hpiao@dicp.ac.cn. FAU - Liang, Rui AU - Liang R AD - Department of General Surgery, Shenzhen University General Hospital/Shenzhen University Clinical Medical Academy, Shenzhen, 518055, China; Carson International Cancer Research Centre, Shenzhen University School of Medicine, Shenzhen, 518055, China. Electronic address: lr9311038@yahoo.com. FAU - Dong, Chengyong AU - Dong C AD - Division of Hepatobiliary and Pancreatic Surgery, Department of General Surgery, The Second Hospital of Dalian Medical University, Dalian, 116027, China. Electronic address: dongchengy@126.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220610 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (PLIN2 protein, human) RN - 0 (Perilipin-2) SB - IM MH - Autophagy/genetics MH - *Carcinoma, Hepatocellular/pathology MH - Cell Line, Tumor MH - Cell Proliferation/genetics MH - Gene Expression Regulation, Neoplastic MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism MH - *Liver Neoplasms/pathology MH - Perilipin-2/metabolism OTO - NOTNLM OT - AMPKalpha OT - Autophagy OT - HCC OT - HIF1alpha OT - PLIN2 EDAT- 2022/06/14 06:00 MHDA- 2022/07/20 06:00 CRDT- 2022/06/13 19:22 PHST- 2020/12/11 00:00 [received] PHST- 2022/05/22 00:00 [revised] PHST- 2022/06/04 00:00 [accepted] PHST- 2022/06/14 06:00 [pubmed] PHST- 2022/07/20 06:00 [medline] PHST- 2022/06/13 19:22 [entrez] AID - S0014-4827(22)00237-3 [pii] AID - 10.1016/j.yexcr.2022.113244 [doi] PST - ppublish SO - Exp Cell Res. 2022 Sep 1;418(1):113244. doi: 10.1016/j.yexcr.2022.113244. Epub 2022 Jun 10.