PMID- 31966484 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200126 IS - 1936-2625 (Electronic) IS - 1936-2625 (Linking) VI - 10 IP - 11 DP - 2017 TI - microRNA-802 is involved in palmitate-induced damage to pancreatic beta cells through repression of sirtuin 6. PG - 11300-11307 AB - Free fatty acid (FFA)-induced pancreatic beta-cell loss is implicated in the pathogenesis of type 2 diabetes mellitus (T2DM). It has been documented that circulating microRNA (miR)-802 levels are significantly greater in T2DM patients than in healthy subjects. However, the role of miR-802 in FFA-induced damage to beta cells is still unclear. In the present study, we measured the expression of miR-802 in the INS-1 rat insulinoma cell line after palmitate treatment for 48 h. Gain- and loss-of-function studies were conducted to determine the function of miR-802 in palmitate-induced apoptosis and reactive oxygen species (ROS) production. The target gene(s) of miR-802 was functionally characterized. Compared to control cells, palmitate treatment caused a time- and concentration-dependent induction of miR-802 in INS-1 cells. Knockdown of miR-802 significantly blocked palmitate-induced apoptosis and attenuated ROS formation. Moreover, miR-802 downregulation prevented the reduction of prosurvival proteins Mcl-1 and Bcl-xL by palmitate. In contrast, ectopic expression of miR-802 stimulated apoptosis and ROS generation in INS-1 cells. Sirtuin 6 (SIRT6) was identified to be a direct target gene of miR-802. Overexpression of miR-802 suppressed the expression of SIRT6. Enforced expression of SIRT6 abolished the induction of apoptosis and ROS production by miR-802. Taken together, miR-802 is required for palmitate-induced damage to beta cells by targeting SIRT6 and represents a potential therapeutic target for T2DM. CI - IJCEP Copyright (c) 2017. FAU - Lin, Ning AU - Lin N AD - Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China. FAU - Niu, Yixin AU - Niu Y AD - Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China. FAU - Zhang, Weiwei AU - Zhang W AD - Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China. FAU - Li, Xiaoyong AU - Li X AD - Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China. FAU - Yang, Zhen AU - Yang Z AD - Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China. FAU - Su, Qing AU - Su Q AD - Department of Endocrinology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China. LA - eng PT - Journal Article DEP - 20171101 PL - United States TA - Int J Clin Exp Pathol JT - International journal of clinical and experimental pathology JID - 101480565 PMC - PMC6965834 OTO - NOTNLM OT - Diabetes OT - SIRT6 OT - free fatty acid OT - miR-802 COIS- None. EDAT- 2017/11/01 00:00 MHDA- 2017/11/01 00:01 PMCR- 2017/11/01 CRDT- 2020/01/23 06:00 PHST- 2017/08/12 00:00 [received] PHST- 2017/10/30 00:00 [accepted] PHST- 2020/01/23 06:00 [entrez] PHST- 2017/11/01 00:00 [pubmed] PHST- 2017/11/01 00:01 [medline] PHST- 2017/11/01 00:00 [pmc-release] PST - epublish SO - Int J Clin Exp Pathol. 2017 Nov 1;10(11):11300-11307. eCollection 2017.