A Set of Circulating MicroRNAs Belonging to the 14q32 Chromosome Locus Identifies Two Subgroups Of individuals with Recent-onset Type 1 Diabetes

Overview

Journal Cell Rep Med

Publisher Cell Press

Specialties Biology
General Medicine

Date 2024 Jun 5

PMID 38838677

Authors

Guido Sebastiani

Giuseppina Emanuela Grieco

Marco Bruttini

Stefano Auddino

Alessia Mori

Mattia Toniolli

Daniela Fignani

Giada Licata

Elena Aiello

Laura Nigi

Caterina Formichi

Juan Fernandez-Tajes

Alberto Pugliese

Carmella Evans-Molina

Lut Overbergh

Timothy Tree

Mark Peakman

Chantal Mathieu

Francesco Dotta

Affiliations

Soon will be listed here.

Abstract

Circulating microRNAs (miRNAs) are linked to the onset and progression of type 1 diabetes mellitus (T1DM), thus representing potential disease biomarkers. In this study, we employed a multiplatform sequencing approach to analyze circulating miRNAs in an extended cohort of prospectively evaluated recent-onset T1DM individuals from the INNODIA consortium. Our findings reveal that a set of miRNAs located within T1DM susceptibility chromosomal locus 14q32 distinguishes two subgroups of individuals. To validate our results, we conducted additional analyses on a second cohort of T1DM individuals, confirming the identification of these subgroups, which we have named cluster A and cluster B. Remarkably, cluster B T1DM individuals, who exhibit increased expression of a set of 14q32 miRNAs, show better glycemic control and display a different blood immunomics profile. Our findings suggest that this set of circulating miRNAs can identify two different T1DM subgroups with distinct blood immunomics at baseline and clinical outcomes during follow-up.

References

Chim S, Shing T, Hung E, Leung T, Lau T, Chiu R . Detection and characterization of placental microRNAs in maternal plasma. Clin Chem. 2008; 54(3):482-90. DOI: 10.1373/clinchem.2007.097972. View

Vignali D, Cantarelli E, Bordignon C, Canu A, Citro A, Annoni A . Detection and Characterization of CD8 Autoreactive Memory Stem T Cells in Patients With Type 1 Diabetes. Diabetes. 2018; 67(5):936-945. DOI: 10.2337/db17-1390. View

den Hollander N, Roep B . From Disease and Patient Heterogeneity to Precision Medicine in Type 1 Diabetes. Front Med (Lausanne). 2022; 9:932086. PMC: 9314738. DOI: 10.3389/fmed.2022.932086. View

Benetatos L, Vartholomatos G, Hatzimichael E . MEG3 imprinted gene contribution in tumorigenesis. Int J Cancer. 2011; 129(4):773-9. DOI: 10.1002/ijc.26052. View

Deligne C, You S, Mallone R . Personalized Immunotherapies for Type 1 Diabetes: Who, What, When, and How?. J Pers Med. 2022; 12(4). PMC: 9031881. DOI: 10.3390/jpm12040542. View

Ferracin M, Negrini M . Quantification of Circulating MicroRNAs by Droplet Digital PCR. Methods Mol Biol. 2018; 1768:445-457. DOI: 10.1007/978-1-4939-7778-9_25. View

Herold K, Bundy B, Long S, Bluestone J, DiMeglio L, Dufort M . An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med. 2019; 381(7):603-613. PMC: 6776880. DOI: 10.1056/NEJMoa1902226. View

Dunger D, Bruggraber S, Mander A, Marcovecchio M, Tree T, Chmura P . INNODIA Master Protocol for the evaluation of investigational medicinal products in children, adolescents and adults with newly diagnosed type 1 diabetes. Trials. 2022; 23(1):414. PMC: 9116021. DOI: 10.1186/s13063-022-06259-z. View

Mathieu C, Lahesmaa R, Bonifacio E, Achenbach P, Tree T . Immunological biomarkers for the development and progression of type 1 diabetes. Diabetologia. 2018; 61(11):2252-2258. DOI: 10.1007/s00125-018-4726-8. View

10.

Assmann T, Duarte G, Brondani L, de Freitas P, Martins E, Canani L . Polymorphisms in genes encoding miR-155 and miR-146a are associated with protection to type 1 diabetes mellitus. Acta Diabetol. 2017; 54(5):433-441. DOI: 10.1007/s00592-016-0961-y. View

11.

Wallace C, Smyth D, Maisuria-Armer M, Walker N, Todd J, Clayton D . The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes. Nat Genet. 2009; 42(1):68-71. PMC: 2820243. DOI: 10.1038/ng.493. View

12.

Smithson M, Verkuilen J . A better lemon squeezer? Maximum-likelihood regression with beta-distributed dependent variables. Psychol Methods. 2006; 11(1):54-71. DOI: 10.1037/1082-989X.11.1.54. View

13.

Krischer J, Liu X, Lernmark A, Hagopian W, Rewers M, She J . The Influence of Type 1 Diabetes Genetic Susceptibility Regions, Age, Sex, and Family History on the Progression From Multiple Autoantibodies to Type 1 Diabetes: A TEDDY Study Report. Diabetes. 2017; 66(12):3122-3129. PMC: 5697938. DOI: 10.2337/db17-0261. View

14.

Grieco G, Sebastiani G, Fignani D, Brusco N, Nigi L, Formichi C . Protocol to analyze circulating small non-coding RNAs by high-throughput RNA sequencing from human plasma samples. STAR Protoc. 2021; 2(3):100606. PMC: 8219884. DOI: 10.1016/j.xpro.2021.100606. View

15.

Wong R, MacMahon M, Woodside J, Simpson D . A comparison of RNA extraction and sequencing protocols for detection of small RNAs in plasma. BMC Genomics. 2019; 20(1):446. PMC: 6547578. DOI: 10.1186/s12864-019-5826-7. View

16.

Assmann T, Recamonde-Mendoza M, Punales M, Tschiedel B, Canani L, Crispim D . MicroRNA expression profile in plasma from type 1 diabetic patients: Case-control study and bioinformatic analysis. Diabetes Res Clin Pract. 2018; 141:35-46. DOI: 10.1016/j.diabres.2018.03.044. View

17.

Erener S, Marwaha A, Tan R, Panagiotopoulos C, Kieffer T . Profiling of circulating microRNAs in children with recent onset of type 1 diabetes. JCI Insight. 2017; 2(4):e89656. PMC: 5313074. DOI: 10.1172/jci.insight.89656. View

18.

Thomou T, Mori M, Dreyfuss J, Konishi M, Sakaguchi M, Wolfrum C . Adipose-derived circulating miRNAs regulate gene expression in other tissues. Nature. 2017; 542(7642):450-455. PMC: 5330251. DOI: 10.1038/nature21365. View

19.

Androvic P, Benesova S, Rohlova E, Kubista M, Valihrach L . Small RNA-Sequencing for Analysis of Circulating miRNAs: Benchmark Study. J Mol Diagn. 2022; 24(4):386-394. DOI: 10.1016/j.jmoldx.2021.12.006. View

20.

Zhou Q, Frost R, Anderson C, Zhao F, Ma J, Yu B . let-7 Contributes to Diabetic Retinopathy but Represses Pathological Ocular Angiogenesis. Mol Cell Biol. 2017; 37(16). PMC: 5533878. DOI: 10.1128/MCB.00001-17. View