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.

Sources:

  • 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.

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