Role of long non-coding RNA in T1DM


Role of long non-coding RNA in T1DM

The precise mechanism that initiates the autoimmune response that leads to type 1 diabetes mellitus (T1DM) is unknown. Many of the genetic associations that have been identified so far are in non-coding regions of the genome; however, their contribution to T1DM pathogenesis has not been studied in detail. A new study has now characterized a long non-coding RNA (lncRNA) that is associated with T1DM.

The researchers focused on alleles of Lnc13, which has previously been associated with T1DM. They used a range of techniques to characterize the lncRNA in vitro. “Moreover, we have also analysed human pancreatic islets to confirm our in vitro results and to determine the impact of a T1DM-associated SNP in Lnc13 in the activation of the inflammatory process,” explain corresponding authors Izortze Santin and Ainara Castellanos-Rubio. “For this purpose, an overexpression vector for Lnc13 harbouring each of the alleles was generated and used throughout the study to test not only downstream effects, but also differential binding of each of the lncRNA forms to the interacting PCBP2 protein and STAT1 mRNA.”

Santin, Castellanos-Rubio and colleagues found that STAT1 expression was increased in human pancreatic islets that had the T1DM-associated Lnc13 risk genotype rs917997*CC compared with islets that had the heterozygous genotype rs917997*CT. Thus, activation of the STAT1 proinflammatory pathway was increased in islets with the risk genotype. “Activation of this pathway in β-cells facilitates the generation of the proinflammatory environment (insulitis) observed in the initial stages of T1DM pathogenesis, and thus, the impact of Lnc13 in this process might be crucial for the progression of the disease,” say Santin and Castellanos-Rubio. The researchers hope that molecular characterization of the T1DM-associated SNPs in non-coding regions will aid the search for novel therapies for T1DM. “In the future, our research group aims to identify novel RNA molecules related to disease-associated variants involved in the development of diseases such as T1DM,” conclude Santin and Castellanos-Rubio.

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