PMID- 36411886 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221123 IS - 2405-8440 (Print) IS - 2405-8440 (Electronic) IS - 2405-8440 (Linking) VI - 8 IP - 11 DP - 2022 Nov TI - Plasma exosomal miR-122 regulates the efficacy of metformin via AMPK in type 2 diabetes and hepatocellular carcinoma. PG - e11503 LID - 10.1016/j.heliyon.2022.e11503 [doi] LID - e11503 AB - Metformin is a drug that has been applied in clinical use for many years for the treatment of type 2 diabetes mellitus (T2DM). It achieves its function through multiple targets and modulation of multiple signaling pathways. To date, the mechanism of the action of metformin is still not fully understood. Along with glycemic control, metformin has shown good inhibitory effects on the development of many tumors. Here, we elucidated that plasma exosomal microRNA-122-5p (miR-122) is closely related to the mechanism of metformin. MiR-122 regulates glycogen-glucose metabolism in hepatocytes or hepatocellular carcinoma cells (HCC) by inhibiting the phosphorylation of AMPK. Since miR-122 and metformin regulate glucose metabolism homeostasis through similar mechanisms, miR-122 can antagonize the effects of metformin. MiR-122 expression increases the sensitivity of hepatocytes or HCC to metformin. Conversely, decreased expression of miR-122 results in hepatocyte insensitivity to metformin. Therefore, significantly elevated levels of miR-122 in plasma exosomes of hepatocellular carcinoma patients could enhance their sensitivity to metformin. The results of the present study revealed a key regulatory role of plasma exosomal miR-122 on the molecular mechanism of metformin. The regulation of key molecules of related signaling pathways by miR-122 may lead to similar glycemic lowering and tumor suppression therapeutic effects as metformin. This provides new ideas for the development of new therapeutic strategies for hepatocellular carcinoma based on the mechanism of miR-122 and metformin. CI - (c) 2022 The Author(s). FAU - Peng, Hui AU - Peng H AD - Department of General Surgery, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, 230031, PR China. AD - Institute of Chinese Medicine Surgery, Anhui Academy of Chinese Medicine, Hefei, Anhui, 230031, PR China. FAU - Hou, Mei AU - Hou M AD - Cancer Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, PR China. FAU - Wu, Zixin AU - Wu Z AD - Cancer Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, PR China. FAU - Wang, Jing AU - Wang J AD - Cancer Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, PR China. FAU - Zhou, Man AU - Zhou M AD - Department of Endocrinology, Wuhan Third Hospital, Wuhan, Hubei 430060, PR China. FAU - Zhuang, Xiangjin AU - Zhuang X AD - Cancer Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, PR China. FAU - Xing, Jiayu AU - Xing J AD - Cancer Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, PR China. FAU - Tao, Qianqian AU - Tao Q AD - Department of General Surgery, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, 230031, PR China. AD - Institute of Chinese Medicine Surgery, Anhui Academy of Chinese Medicine, Hefei, Anhui, 230031, PR China. FAU - Huang, Long AU - Huang L AD - Department of General Surgery, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, 230031, PR China. AD - Institute of Chinese Medicine Surgery, Anhui Academy of Chinese Medicine, Hefei, Anhui, 230031, PR China. FAU - Zhou, Fuhai AU - Zhou F AD - Department of General Surgery, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, 230031, PR China. AD - Institute of Chinese Medicine Surgery, Anhui Academy of Chinese Medicine, Hefei, Anhui, 230031, PR China. FAU - Zhang, Shengming AU - Zhang S AD - Department of General Surgery, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, 230031, PR China. AD - Institute of Chinese Medicine Surgery, Anhui Academy of Chinese Medicine, Hefei, Anhui, 230031, PR China. FAU - Feng, Qiyu AU - Feng Q AD - Cancer Research Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230036, PR China. FAU - Hou, Yilin AU - Hou Y AD - Department of Endocrinology, Wuhan Third Hospital, Wuhan, Hubei 430060, PR China. FAU - Yu, Qinsheng AU - Yu Q AD - Department of General Surgery, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, 230031, PR China. AD - Institute of Chinese Medicine Surgery, Anhui Academy of Chinese Medicine, Hefei, Anhui, 230031, PR China. LA - eng PT - Journal Article DEP - 20221114 PL - England TA - Heliyon JT - Heliyon JID - 101672560 PMC - PMC9674877 OTO - NOTNLM OT - AMPK OT - Exosome OT - Hepatocellular carcinoma OT - Metformin OT - Type 2 diabetes OT - miR-122 COIS- The authors declare no conflict of interest. EDAT- 2022/11/23 06:00 MHDA- 2022/11/23 06:01 PMCR- 2022/11/14 CRDT- 2022/11/22 01:49 PHST- 2022/04/30 00:00 [received] PHST- 2022/08/25 00:00 [revised] PHST- 2022/11/01 00:00 [accepted] PHST- 2022/11/22 01:49 [entrez] PHST- 2022/11/23 06:00 [pubmed] PHST- 2022/11/23 06:01 [medline] PHST- 2022/11/14 00:00 [pmc-release] AID - S2405-8440(22)02791-8 [pii] AID - e11503 [pii] AID - 10.1016/j.heliyon.2022.e11503 [doi] PST - epublish SO - Heliyon. 2022 Nov 14;8(11):e11503. doi: 10.1016/j.heliyon.2022.e11503. eCollection 2022 Nov.