MicroRNA-155 promotes apoptosis of colonic smooth muscle cells and aggravates colonic dysmotility by targeting IGF-1.

Colonic dysmotility as a complication of diabetes affects public health; however, the underlying molecular mechanisms have remained elusive. Insulin-like growth factor-1 (IGF-1) was previously demonstrated to prevent apoptosis of colonic smooth muscle cells (SMCs) and alleviate colonic dysmotility in diabetic rats. However, the regulatory mechanisms upstream of IGF-1 in colonic dysmotility have remained to be determined. The present study reports on microRNA-155 (miR-155), initially identified using bioinformatics, as a direct upstream regulator of IGF-1. In colonic SMCs, miR-155 negatively regulated IGF-1 expression at the post-transcriptional level, as identified through ectopic overexpression and knockdown experiments. A luciferase reporter assay further demonstrated that miR-155 inhibits IGF-1 through binding to its 3'-untranslated region. Furthermore, overexpression of miR-155 led to increased apoptosis of colonic SMCs and a decrease in the thickness of colonic smooth muscle tissues of diabetic mice, indicating miR-155 aggravates colonic dysmotility. By contrast, knockdown of miR-155 induced the opposite effect. Overall, the results of the present study suggest a role of miR-155 in colonic dysmotility, thereby providing a novel therapeutic target.