cellular neighborhood: micro pieces

The ‘Micro’ pieces in the T1D puzzle

After confirming its striking relevance to humans, MicroRNA (miRNA) research piqued the interest of researchers who thought miRNA may be a missing puzzle piece to elucidating the development, progression and even treatment of a number of incredibly complex human diseases. Over the last 20 years, research has found hard evidence that miRNAs are in fact connected to a number of diseases in their pathogenesis and as biomarkers — including cancer, Alzheimer’s and T1D.

Before we dive in, let’s take a step back. MiRNAs are non-coding, single-stranded RNA molecules around 22 nucleotides long — but what do they do?

  • miRNAs regulate the expression of particular cellular gene targets.
  • miRNA species can have multiple target genes and regulate overlapping genes, causing an intricate regulatory network.
  • Finally, miRNAs are considered to be consistent and reliable biomarkers for human diseases because they are: 1.) stable, 2.) resistant to degradation by ribonucleases and 3) easily detected.

Why miRNAs matter for T1D

Many studies have reported the dysregulation of a number of miRNAs in those with T1D. Unfortunately, study parameter differences made it difficult to come to a general consensus about which miRNAs are actually implicated in T1D. Luckily, one study conducted an in-depth systematic review and bioinformatic analysis of T1D miRNA literature and discovered the following:

  • Of the hundreds of miRNAs discussed in the collected studies, just 11 miRNA species were consistently dysregulated in individuals with T1D.
  • Next, using the Kyoto Encyclopedia for Genes and Genomes (KEGG) database, the researchers found the biological pathways associated with the miRNA target genes.

“Micro” pieces to T1D

    • miR-21-5p is involved with the immune system, specifically in increasing T-cell production, as well as regulating T-reg development and macrophage anti-inflammatory responses.
      • In T1D, miR-21-5p was overexpressed, augmenting cell death after exposure to pro-inflammatory cytokines and thus reducing the number of beta cells.


  • miR-181a-5p is also involved in immunity by regulating T-cell function and receptor signaling pathways.


    • In T1D onset, miR-181a-5p seems to boost T cell activation of CD4+ T cells, thus promoting pancreatic islet autoimmunity and impairing insulin-specific regulatory T-cell induction.

What’s ahead?

Using miRNAs as targets for T1D treatment has yet to occur, however a few companies including Regulus, Miragen and Synlogic are leading the way for miRNA treatments of other diseases. With T1D researchers’ increased curiosity, miRNA therapies for T1D could be soon underway.


  • Assmann, T. S., Recamonde-Mendoza, M., De Souza, B. M., & Crispim, D. (2017). MicroRNA expression profiles and type 1 diabetes mellitus: systematic review and bioinformatic analysis. Endocrine connections, 6(8), 773-790.
  • Li, Y., & Kowdley, K. V. (2012). MicroRNAs in common human diseases. Genomics, proteomics & bioinformatics, 10(5), 246-253.
  • Miao, C., Chang, J., Zhang, G., & Fang, Y. (2018). MicroRNAs in type 1 diabetes: new research progress and potential directions. Biochemistry and Cell Biology, 96(5), 498-506.
  • Serr, I., Scherm, M. G., Zahm, A. M., Schug, J., Flynn, V. K., Hippich, M., … & Gerlach, K. (2018). A miRNA181a/NFAT5 axis links impaired T cell tolerance induction with autoimmune type 1 diabetes. Science translational medicine, 10(422), eaag1782.