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

作者：Danping Sun, Lingqi Gong, Xiaotong Wang, Shuijiao Chen, Jun Yi, Xiaowei Liu · 发表于：Inflammatory Bowel Diseases · 年份：2023 · DOI：10.1093/ibd/izad105 · 被引用次数：11 · 研究领域：MicroRNA in disease regulation、Biomarkers in Disease Mechanisms、Extracellular vesicles in disease

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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 i...