Pro-inflammatory Cytokines Promote the Occurrence and Development of Colitis-associated Colorectal Cancer by Inhibiting miR-615-5p.

Abstract

Patients with ulcerative colitis (UC) may be prone to colitis-associated colorectal cancer (CAC), but there is still a poor understanding of the underlying mechanism so far. This study intended to clarify the role of pro-inflammatory cytokines and miR-615-5p in this process. This experiment first detected miR-615-5p expressions in paraffin-embedded sections of colonic tissues from patients with UC and CAC. Then, we investigated the mechanism through which pro-inflammatory cytokines affected miR-615-5p. Furthermore, in vivo and in vitro tests were performed to identify how miR-615-5p affected colorectal cancer (CRC). Dual-luciferase reporter assay was then employed to identify the targeting relationship between miR-615-5p and stanniocalcin-1 (STC1). The miR-615-5p was lowly expressed in both cancerous and noncancerous colonic tissues of patients with CAC. Pro-inflammatory cytokines downregulated miR-615-5p expression. Overexpression of miR-615-5p reduced the proliferation and migration of CRC cells and had a certain therapeutic effect on in human CRC xenograft mice. Stanniocalcin-1 was identified to be a target gene of miR-615-5p and was involved in the effect of miR-615-5p on CRC. During the progression from UC to CAC, pro-inflammatory cytokines downregulate miR-615-5p, which may induce the upregulation of STC1, and promote the occurrence and development of tumors. These findings offer new insights into the mechanism of CAC and may indicate novel tumor markers or therapeutic targets.