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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1376416
This article is part of the Research Topic Autoimmune Diseases in Childhood View all 23 articles

Circulating hsa-miR-320a and its regulatory network in type 1 diabetes mellitus

Provisionally accepted
Rasheeba Nizam Rasheeba Nizam 1Md Zubbair Malik Md Zubbair Malik 1Sindhu Jacob Sindhu Jacob 1Osama Alsmadi Osama Alsmadi 1Heikki A. Koistinen Heikki A. Koistinen 2Jaakko Tuomilehto Jaakko Tuomilehto 2Hessa AlKandari Hessa AlKandari 1Fahd Al Mulla Fahd Al Mulla 1*Alphonse T. Thangavel Alphonse T. Thangavel 1*
  • 1 Dasman Diabetes Institute, Kuwait City, Kuwait
  • 2 University of Helsinki, Helsinki, Uusimaa, Finland

The final, formatted version of the article will be published soon.

    Increasing evidence from human and animal model studies indicates the significant role of microRNAs (miRNAs) in pancreatic beta cell function, insulin signaling, immune responses, and pathogenesis of type 1 diabetes (T1D). We aimed, using next-generation sequencing, to screen miRNAs from peripheral blood mononuclear cells of eight independent Kuwaiti-Arab families with T1D affected siblings, consisting of 18 T1D patients and 18 unaffected members, characterized by no parent-to-child inheritance pattern. Our analysis revealed 20 miRNAs that are differentially expressed in T1D patients compared with healthy controls. Module-based weighted gene co-expression network analysis prioritized key consensus miRNAs in T1D pathogenesis. These included hsa-miR-320a-3p, hsa-miR-139-3p, hsa-miR-200-3p, hsa-miR-99b-5p and has-miR-6808-3p. Functional enrichment analysis of differentially expressed miRNAs indicated that PI3K-AKT is one of the key pathways perturbed in T1D. Gene ontology analysis of hub miRNAs also implicated PI3K-AKT, along with mTOR, MAPK, and interleukin signaling pathways, in T1D. Using quantitative RT-PCR, we validated one of the key predicted miRNA-target gene-transcription factor networks in an extended cohort of children with new-onset T1D positive for islet autoantibodies. Our analysis revealed that hsa-miR-320a-3p and its key targets, including PTEN, AKT1, BCL2, FOXO1 and MYC, are dysregulated in T1D, along with their interacting partners namely BLIMP3, GSK3B, CAV1, CXCL3, TGFB, and IL10. Receiver Operating Characteristic analysis highlighted the diagnostic potential of hsa-miR-320a-3p, CAV1, GSK3B and MYC for T1D. Our study presents a novel link between hsa-miR-320a-3p and T1D, and highlights its key regulatory role in the network of miRNA markers and transcription factors involved in T1D pathogenesis.

    Keywords: hsa-miR-320a-3p, miRNA, type 1 diabetes, Kuwait, Genetics, Next-generation sequencing, weighted gene co-expression network analysis

    Received: 25 Jan 2024; Accepted: 26 Sep 2024.

    Copyright: © 2024 Nizam, Malik, Jacob, Alsmadi, Koistinen, Tuomilehto, AlKandari, Al Mulla and Thangavel. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Fahd Al Mulla, Dasman Diabetes Institute, Kuwait City, Kuwait
    Alphonse T. Thangavel, Dasman Diabetes Institute, Kuwait City, Kuwait

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