PMID- 35598373 OWN - NLM STAT- MEDLINE DCOM- 20220608 LR - 20220608 IS - 1950-6007 (Electronic) IS - 0753-3322 (Linking) VI - 151 DP - 2022 Jul TI - The role of MicroRNA networks in tissue-specific direct and indirect effects of metformin and its application. PG - 113130 LID - S0753-3322(22)00519-4 [pii] LID - 10.1016/j.biopha.2022.113130 [doi] AB - Metformin is a first-line oral antidiabetic agent that results in clear benefits in relation to glucose metabolism and diabetes-related complications. The specific regulatory details and mechanisms underlying these benefits are still unclear and require further investigation. There is recent mounting evidence that metformin has pleiotropic effects on the target tissue development in metabolic organs, including adipose tissue, the gastrointestinal tract and the liver. The mechanism of actions of metformin are divided into direct effects on target tissues and indirect effects via non-targeted tissues. MicroRNAs (miRNAs) are a class of endogenous, noncoding, negative gene regulators that have emerged as important regulators of a number of diseases, including type 2 diabetes mellitus (T2DM). Metformin is involved in many aspects of miRNA regulation, and metformin treatment in T2DM should be associated with other miRNA targets. A large number of miRNAs regulation by metformin in target tissues with either direct or indirect effects has gradually been revealed in the context of numerous diseases and has gradually received increasing attention. This paper thoroughly reviews the current knowledge about the role of miRNA networks in the tissue-specific direct and indirect effects of metformin. Furthermore, this knowledge provides a novel theoretical basis and suggests therapeutic targets for the clinical treatment of metformin and miRNA regulators in the prevention and treatment of cancer, cardiovascular disorders, diabetes and its complications. CI - Copyright (c) 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved. FAU - Yang, Qinzhi AU - Yang Q AD - Key Laboratory of Medical Electrophysiology, Ministry of Education, Drug Discovery Research Center, Southwest Medical University, Luzhou, China; Laboratory for Cardiovascular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China. FAU - Wang, Gang AU - Wang G AD - School of Pharmacy, Chongqing Medical University, Chongqing, China. FAU - Fang, Dan AU - Fang D AD - Key Laboratory of Medical Electrophysiology, Ministry of Education, Drug Discovery Research Center, Southwest Medical University, Luzhou, China; Laboratory for Cardiovascular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China. FAU - Gao, Xiaojun AU - Gao X AD - Key Laboratory of Medical Electrophysiology, Ministry of Education, Drug Discovery Research Center, Southwest Medical University, Luzhou, China; Laboratory for Cardiovascular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China. FAU - Liang, Yu AU - Liang Y AD - Integrated Traditional Chinese and Western Medicine, Affiliated Hospital of Traditional Chinese Medicine, Southwest Medical University, Luzhou, Sichuan, China. FAU - Wang, Liqun AU - Wang L AD - Key Laboratory of Medical Electrophysiology, Ministry of Education, Drug Discovery Research Center, Southwest Medical University, Luzhou, China; Laboratory for Cardiovascular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China. FAU - Wu, Jianbo AU - Wu J AD - Key Laboratory of Medical Electrophysiology, Ministry of Education, Drug Discovery Research Center, Southwest Medical University, Luzhou, China; Laboratory for Cardiovascular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China. FAU - Zeng, Min AU - Zeng M AD - Department of Pharmacy, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. Electronic address: zengminlz@163.com. FAU - Luo, Mao AU - Luo M AD - Key Laboratory of Medical Electrophysiology, Ministry of Education, Drug Discovery Research Center, Southwest Medical University, Luzhou, China; Laboratory for Cardiovascular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China; Integrated Traditional Chinese and Western Medicine, Affiliated Hospital of Traditional Chinese Medicine, Southwest Medical University, Luzhou, Sichuan, China; Department of Pharmacy, the Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. Electronic address: luomao20050908@163.com. LA - eng PT - Journal Article PT - Review DEP - 20220520 PL - France TA - Biomed Pharmacother JT - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JID - 8213295 RN - 0 (Hypoglycemic Agents) RN - 0 (MicroRNAs) RN - 9100L32L2N (Metformin) SB - IM MH - *Diabetes Mellitus, Type 2/drug therapy/genetics/metabolism MH - Humans MH - Hypoglycemic Agents/pharmacology/therapeutic use MH - *Metformin/pharmacology/therapeutic use MH - *MicroRNAs/metabolism MH - *Neoplasms/drug therapy OTO - NOTNLM OT - Metformin OT - MicroRNAs OT - Therapeutic application OT - Tissue-specific direct and indirect effects EDAT- 2022/05/23 06:00 MHDA- 2022/06/09 06:00 CRDT- 2022/05/22 18:08 PHST- 2022/03/23 00:00 [received] PHST- 2022/05/06 00:00 [revised] PHST- 2022/05/13 00:00 [accepted] PHST- 2022/05/23 06:00 [pubmed] PHST- 2022/06/09 06:00 [medline] PHST- 2022/05/22 18:08 [entrez] AID - S0753-3322(22)00519-4 [pii] AID - 10.1016/j.biopha.2022.113130 [doi] PST - ppublish SO - Biomed Pharmacother. 2022 Jul;151:113130. doi: 10.1016/j.biopha.2022.113130. Epub 2022 May 20.