@article{35c5c656e31e4d42a4ef1f07cef88c89,
title = "miRNA-642a-3p protects {\ss} cells from glucolipotoxicity",
abstract = "The incidence of type 2 diabetes mellitus (T2DM) is tightly linked to obesity. High levels of circulating glucose and saturated free fatty acids (FFAs), known as glucolipotoxicity (GLT), is implicated in {\ss} cell dysfunction and/or death. This study aims to identify miRNAs capable of protecting {\ss} cells from GLT-induced cell death (GICD). A library of 2,080 human miRNA mimics was transfected in {\ss} cells followed by exposure to GLT. We identified 45 miRNAs capable of protecting {\ss} cells from GICD and selected miR-642a-3p for further studies. RNA-seq revealed that miR-642a-3p restored the expression of {\ss} cell identity genes and modulated pathways associated with cell survival and lipid metabolism. Moreover, we showed that transfection of {\ss} cells with miR-642a-3p protected them from GLT-induced changes in insulin secretion. Compared with the control, hypercaloric-fed mice showed a trend toward decreased expression of GLT-protective miRNAs. Notably, we demonstrated that miR-642a-3p expression was downregulated in human islets isolated from T2DM patients compared with non-diabetic controls. Importantly, in obese patients, the expression of GLT-protective miRNAs in plasma-derived extracellular vesicles was increased in non-diabetic patients. Overall, we have identified a potential dual role for miR-642a-3p as both a biomarker and a facilitator of {\ss} cell survival and function, offering a novel theranostic tool for the management of diabetes and/or obesity.",
keywords = "bariatric surgery, diabetes, extracellular vesicles, glucolipotoxicity, microRNAs, MT: Non-coding RNAs, obesity, {\ss} cells",
author = "Pinhan{\c c}os, {Sandra Sofia} and {Teixeira de Oliveira}, Jo{\~a}o and Alves, {C. Henrique} and Deus, {Cl{\'a}udia M.} and {de Winter}, {Twan J.J.} and Sofia Viana and Fl{\'a}vio Reis and Jorge Santos and Mijke Buitinga and Fran{\c c}oise Carlotti and Lino Ferreira and Martin Gotthardt and John Jones and Hugo Fernandes",
note = "Funding Information: This work was supported by The Netherlands Organisation for Health Research and Development (ZonMW, reference 95105008), \u201CBIO-MED: Engenharia Biomolecular de Ves\u00EDculas Extracelulares para Medicina Regenerative\u201D (reference CENTRO-01-0145-FEDER-181228), Twinning RESETAgeing (Ref:952266), SPD \u2013 Sociedade Portuguesa De Diabetologia, Grupo de Estudos de Investiga\u00E7\u00E3o Fundamental e Translacional (GIFT), and MIA-Portugal (this project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement no. 857524). S.S.P. was supported by FCT (SFRH/BD/144119/2019), HF CEECIND/01880/2018, CHA CEECIND/2022.00041. C.D., C.H.A., F.R., L.F., J.J., and H.F. acknowledge support from FCT/MCTES (CIBB strategic project UIDP/04539/2020) and European Union's Horizon Europe program (Excellence Hubs \u2013 HORIZON-WIDERA-2022-ACCESS-04-01), under the grant agreement #101087071. Funding Information: This work was supported by The Netherlands Organisation for Health Research and Development (ZonMW, reference 95105008 ), \u201C BIO-MED: Engenharia Biomolecular de Ves\u00EDculas Extracelulares para Medicina Regenerative \u201D (reference CENTRO-01-0145-FEDER-181228 ), Twinning RESETAgeing (Ref: 952266 ), SPD \u2013 Sociedade Portuguesa De Diabetologia , Grupo de Estudos de Investiga\u00E7\u00E3o Fundamental e Translacional (GIFT), and MIA-Portugal . This project has received funding from the European Union\u2019s Horizon 2020 research and innovation programme under grant agreement no. 857524 . S.M.P. was supported by FCT ( SFRH/BD/144119/2019 ), HF CEECIND/01880/2018 , CHA CEECIND/2022.00041 . Publisher Copyright: {\textcopyright} 2025 The Authors",
year = "2025",
month = jan,
day = "1",
doi = "10.1016/j.omtn.2025.102498",
language = "English",
journal = "Molecular Therapy - Nucleic Acids",
issn = "2162-2531",
publisher = "Cell Press",
}