Global miRNA expression reveals novel nuclear and mitochondrial interactions in Type 1 diabetes mellitus.

Autor:	Ferraz RS; Laboratory of Human and Medical Genetics, Graduate Program in Genetics and Molecular Biology, Federal University of Para, Belem, PA, Brazil., Santos LCB; Laboratory of Human and Medical Genetics, Graduate Program in Genetics and Molecular Biology, Federal University of Para, Belem, PA, Brazil., da-Silva-Cruz RL; Laboratory of Human and Medical Genetics, Graduate Program in Genetics and Molecular Biology, Federal University of Para, Belem, PA, Brazil., Braga-da-Silva CH; Laboratory of Human and Medical Genetics, Graduate Program in Genetics and Molecular Biology, Federal University of Para, Belem, PA, Brazil., Magalhães L; Laboratory of Human and Medical Genetics, Graduate Program in Genetics and Molecular Biology, Federal University of Para, Belem, PA, Brazil., Ribeiro-Dos-Santos A; Laboratory of Human and Medical Genetics, Graduate Program in Genetics and Molecular Biology, Federal University of Para, Belem, PA, Brazil., Vidal A; Laboratory of Human and Medical Genetics, Graduate Program in Genetics and Molecular Biology, Federal University of Para, Belem, PA, Brazil.; Instituto Tecnológico Vale Desenvolvimento Sustentável Vale, Institute of Technology, Belem, PA, Brazil., Vinasco-Sandoval T; Laboratoire de Génomique et Radiobiologie de la Kératinopoïèse, Institut de Biologie François Jacob, CEA/DRF/IRCM, Evry, France., Reis-das-Mercês L; Laboratory of Human and Medical Genetics, Graduate Program in Genetics and Molecular Biology, Federal University of Para, Belem, PA, Brazil., Sena-Dos-Santos C; Laboratory of Human and Medical Genetics, Graduate Program in Genetics and Molecular Biology, Federal University of Para, Belem, PA, Brazil., Pereira AL; Medical School, Federal University of Para, Altamira, PA, Brazil., Silva LSD; Endocrinology Research Center, Joao de Barros Barreto University Hospital, Federal University of Para, Belem, PA, Brazil., de Melo FTC; Endocrinology Research Center, Joao de Barros Barreto University Hospital, Federal University of Para, Belem, PA, Brazil., de Souza ACCB; Endocrinology Research Center, Joao de Barros Barreto University Hospital, Federal University of Para, Belem, PA, Brazil., Leal VSG; Endocrinology Research Center, Joao de Barros Barreto University Hospital, Federal University of Para, Belem, PA, Brazil., de Figueiredo PBB; Endocrinology Research Center, Joao de Barros Barreto University Hospital, Federal University of Para, Belem, PA, Brazil., Neto JFA; Endocrinology Research Center, Joao de Barros Barreto University Hospital, Federal University of Para, Belem, PA, Brazil., de Moraes LV; Endocrinology Research Center, Joao de Barros Barreto University Hospital, Federal University of Para, Belem, PA, Brazil., de Lemos GN; Endocrinology Research Center, Joao de Barros Barreto University Hospital, Federal University of Para, Belem, PA, Brazil., de Queiroz NNM; Endocrinology Research Center, Joao de Barros Barreto University Hospital, Federal University of Para, Belem, PA, Brazil., Felício KM; Endocrinology Research Center, Joao de Barros Barreto University Hospital, Federal University of Para, Belem, PA, Brazil., Cavalcante GC; Laboratory of Human and Medical Genetics, Graduate Program in Genetics and Molecular Biology, Federal University of Para, Belem, PA, Brazil., Ribeiro-Dos-Santos Â; Laboratory of Human and Medical Genetics, Graduate Program in Genetics and Molecular Biology, Federal University of Para, Belem, PA, Brazil.; Oncology Research Center, Graduate Program in Oncology and Medical Sciences, Joao de Barros Barreto University Hospital, Federal University of Para, Belem, PA, Brazil., Felício JS; Endocrinology Research Center, Joao de Barros Barreto University Hospital, Federal University of Para, Belem, PA, Brazil.
Jazyk:	angličtina
Zdroj:	Frontiers in endocrinology [Front Endocrinol (Lausanne)] 2022 Nov 24; Vol. 13, pp. 1033809. Date of Electronic Publication: 2022 Nov 24 (Print Publication: 2022).
DOI:	10.3389/fendo.2022.1033809
Abstrakt:	Background: Considering the potential role of miRNAs as biomarkers and their interaction with both nuclear and mitochondrial genes, we investigated the miRNA expression profile in type 1 diabetes (T1DM) patients, including the pathways in which they are involved considering both nuclear and mitochondrial functions. Methods: We analyzed samples of T1DM patients and control individuals (normal glucose tolerance) by high throughput miRNA sequencing (miRNome). Next, five miRNAs - hsa-miR-26b-5p , hsa-let-7i-5p , hsa-miR-143-3p , hsa-miR-501-3p and hsa-miR-100-5p - were validated by RT-qPCR. The identification of target genes was extracted from miRTarBase and mitoXplorer database. We also performed receiver operating characteristic (ROC) curves and miRNAs that had an AUC > 0.85 were considered potential biomarkers. Results: Overall, 41 miRNAs were differentially expressed in T1DM patients compared to control. Hsa-miR-21-5p had the highest number of predicted target genes and was associated with several pathways, including insulin signaling and apoptosis. 34.1% (14/41) of the differentially expressed miRNAs also targeted mitochondrial genes, and 80.5% (33/41) of them targeted nuclear genes involved in the mitochondrial metabolism. All five validated miRNAs were upregulated in T1DM. Among them, hsa-miR-26b-5p showed AUC>0.85, being suggested as potential biomarker to T1DM. Conclusion: Our results demonstrated 41 DE miRNAs that had a great accuracy in discriminating T1DM and control group. Furthermore, we demonstrate the influence of these miRNAs on numerous metabolic pathways, including mitochondrial metabolism. Hsa-miR-26b-5p and hsa-miR-21-5p were highlighted in our results, possibly acting on nuclear and mitochondrial dysfunction and, subsequently, T1DM dysregulation. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Ferraz, Santos, da-Silva-Cruz, Braga-da-Silva, Magalhães, Ribeiro-dos-Santos, Vidal, Vinasco-Sandoval, Reis-das-Mercês, Sena-dos-Santos, Pereira, Silva, Melo, Souza, Leal, Figueiredo, Neto, Moraes, Lemos, Queiroz, Felício, Cavalcante, Ribeiro-dos-Santos and Felício.)
Databáze:	MEDLINE
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