Circular RNA MTCL1 targets SMAD3 by sponging miR‐145‐5p for regulation of cell proliferation and migration in Hirschsprung’s disease

Abstract

Abstract Background Hirschsprung’s disease (HSCR) is a congenital disorder due to abnormal development of the enteric nervous system (ENS). Given the complexity of its pathogenesis, it is important to investigate the role of epigenetic inheritance in its development. As Circ-MTCL1 is abundant in brain tissue and colon tissue, whether it has a significant part in the development of ENS is worth exploring. This study clarifies its role in HSCR and determines the specific molecular mechanisms.Methods Diseased and dilated segment colon tissues diagnosed as HSCR were gathered, and the expression level of genes was detected using RT-PCR. EdU and CCK-8 assays were adopted to evaluate cell proliferation, and Transwell assay was adopted to assess cell migration. The interaction between Circ-MTCL1, miR-145-5p and SMAD3 was confirmed by dual luciferase reporter gene analysis, RT-PCR and Western blotting.Results The expression of Circ-MTCL1 was down-regulated in HSCR diseased segment colon tissues. The low expression of Circ-MTCL1 caused a reduction in cell migration and proliferation. Bioinformatics analysis and cellular experiments confirmed that its action may be related to the inhibition of miR-145-5p. The expression of miR-145-5p was up-regulated in HSCR diseased segment colon tissues, which was negatively correlated with Circ-MTCL1. The overexpression of miR-145-5p reversed the suppressive effect of Circ-MTCL1 down-regulation on cell migration and proliferation. The overexpression of miR-145-5p eliminated the suppressive effect on cell migration and proliferation. The expression of SMAD3 was inhibited by MiR-145-5p. The overexpression of SMAD3 eliminated the suppressive effect of miR-145-5p on cell migration and proliferation.Conclusions Circ-MTCL1 may function as a miR-145-5p sponge for regulating the expression of SMAD3 and affect cell migration and proliferation to participate in the development of HSCR.