PMID- 33212990 OWN - NLM STAT- MEDLINE DCOM- 20210303 LR - 20210303 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 21 IP - 22 DP - 2020 Nov 17 TI - miR-27b Modulates Insulin Signaling in Hepatocytes by Regulating Insulin Receptor Expression. LID - 10.3390/ijms21228675 [doi] LID - 8675 AB - Insulin resistance (IR) is one of the key contributing factors in the development of type 2 diabetes mellitus (T2DM). However, the molecular mechanisms leading to IR are still unclear. The implication of microRNAs (miRNAs) in the pathophysiology of multiple cardiometabolic pathologies, including obesity, atherosclerotic heart failure and IR, has emerged as a major focus of interest in recent years. Indeed, upregulation of several miRNAs has been associated with obesity and IR. Among them, miR-27b is overexpressed in the liver in patients with obesity, but its role in IR has not yet been thoroughly explored. In this study, we investigated the role of miR-27b in regulating insulin signaling in hepatocytes, both in vitro and in vivo. Therefore, assessment of the impact of miR-27b on insulin resistance through the hepatic tissue is of special importance due to the high expression of miR-27b in the liver together with its known role in regulating lipid metabolism. Notably, we found that miR-27b controls post-transcriptional expression of numerous components of the insulin signaling pathway including the insulin receptor (INSR) and insulin receptor substrate 1 (IRS1) in human hepatoma cells. These results were further confirmed in vivo showing that overexpression and inhibition of hepatic miR-27 enhances and suppresses hepatic INSR expression and insulin sensitivity, respectively. This study identified a novel role for miR-27 in regulating insulin signaling, and this finding suggests that elevated miR-27 levels may contribute to early development of hepatic insulin resistance. FAU - Benito-Vicente, Asier AU - Benito-Vicente A AUID- ORCID: 0000-0003-1653-1722 AD - Biofisika Institute (UPV/EHU, CSIC) and Departamento de Bioquimica, Universidad del Pais Vasco, 48940 Leioa, Spain. FAU - Uribe, Kepa B AU - Uribe KB AUID- ORCID: 0000-0002-4502-4853 AD - Biofisika Institute (UPV/EHU, CSIC) and Departamento de Bioquimica, Universidad del Pais Vasco, 48940 Leioa, Spain. FAU - Rotllan, Noemi AU - Rotllan N AUID- ORCID: 0000-0002-0587-8045 AD - Vascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT 06520-8066, USA. FAU - Ramirez, Cristina M AU - Ramirez CM AD - Vascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT 06520-8066, USA. AD - IMDEA Research Institute of Food and Health Sciences, 28049 Madrid, Spain. FAU - Jebari-Benslaiman, Shifa AU - Jebari-Benslaiman S AD - Biofisika Institute (UPV/EHU, CSIC) and Departamento de Bioquimica, Universidad del Pais Vasco, 48940 Leioa, Spain. FAU - Goedeke, Leigh AU - Goedeke L AD - Vascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT 06520-8066, USA. FAU - Canfran-Duque, Alberto AU - Canfran-Duque A AD - Vascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT 06520-8066, USA. FAU - Galicia-Garcia, Unai AU - Galicia-Garcia U AD - Biofisika Institute (UPV/EHU, CSIC) and Departamento de Bioquimica, Universidad del Pais Vasco, 48940 Leioa, Spain. AD - Fundacion Biofisika Bizkaia, 48940 Leioa, Spain. FAU - Saenz De Urturi, Diego AU - Saenz De Urturi D AD - Department of Physiology, Faculty of Medicine and Nursing, University of Basque Country UPV/EHU, 48940 Leioa, Spain. FAU - Aspichueta, Patricia AU - Aspichueta P AD - Department of Physiology, Faculty of Medicine and Nursing, University of Basque Country UPV/EHU, 48940 Leioa, Spain. FAU - Suarez, Yajaira AU - Suarez Y AD - Vascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT 06520-8066, USA. FAU - Fernandez-Hernando, Carlos AU - Fernandez-Hernando C AD - Vascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine and Department of Pathology, Yale University School of Medicine, New Haven, CT 06520-8066, USA. FAU - Martin, Cesar AU - Martin C AUID- ORCID: 0000-0002-4087-8729 AD - Biofisika Institute (UPV/EHU, CSIC) and Departamento de Bioquimica, Universidad del Pais Vasco, 48940 Leioa, Spain. LA - eng PT - Journal Article DEP - 20201117 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (IRS1 protein, human) RN - 0 (Insulin) RN - 0 (Insulin Receptor Substrate Proteins) RN - 0 (MIRN27b microRNA, human) RN - 0 (MicroRNAs) RN - EC 2.7.10.1 (Receptor, Insulin) SB - IM MH - Cell Line MH - Hepatocytes/cytology/*metabolism MH - Humans MH - Insulin/genetics/*metabolism MH - Insulin Receptor Substrate Proteins/genetics/metabolism MH - MicroRNAs/genetics/metabolism MH - Receptor, Insulin/genetics/*metabolism MH - *Signal Transduction PMC - PMC7698485 OTO - NOTNLM OT - INRS OT - insulin signaling OT - miR-27b OT - microRNA OT - type 2 diabetes mellitus COIS- The authors declare no conflict of interest. EDAT- 2020/11/21 06:00 MHDA- 2021/03/04 06:00 PMCR- 2020/11/01 CRDT- 2020/11/20 01:01 PHST- 2020/10/21 00:00 [received] PHST- 2020/11/14 00:00 [revised] PHST- 2020/11/16 00:00 [accepted] PHST- 2020/11/20 01:01 [entrez] PHST- 2020/11/21 06:00 [pubmed] PHST- 2021/03/04 06:00 [medline] PHST- 2020/11/01 00:00 [pmc-release] AID - ijms21228675 [pii] AID - ijms-21-08675 [pii] AID - 10.3390/ijms21228675 [doi] PST - epublish SO - Int J Mol Sci. 2020 Nov 17;21(22):8675. doi: 10.3390/ijms21228675.