MiR-873-5p suppresses cell proliferation and epithelial-mesenchymal transition via directly targeting Jumonji domain-containing protein 8 through the NF-kappa B pathway in colorectal cancer

摘要

Colorectal cancer (CRC) is one of the most common leading causes of cancer-related deaths in the world. Recent studies showed that microRNAs (miRNAs) play important roles in the development of diseases, such as CRC. However, the role of miR-873-5p in CRC remains unclear. In this study, we found that miR-873-5p expression was down-regulated in CRC tissues and cell lines, and the down-regulation of miR-873-5p expression was associated with poor survival in patients with CRC. MiR-873-5p could function as a tumour suppressor in CRC. It could inhibit the growth, proliferation, migration and invasion of CRC cells; influence the cell cycle and enhance apoptosis of CRC cells. Bioinformatics and luciferase reporter analyses demonstrated that Jumonji domain-containing protein 8 (JMJD8) was a target of miR-873-5p that could directly target the 3'UTR of JMJD8 and significantly inhibit its expression in CRC cells. This study also verified that JMJD8 functioned as an oncogene in CRC cells. The over-expression of JMJD8 could partly save the harmful effects induced by miR-873-5p in CRC cells, demonstrating that miR-873-5p suppressed carcinogenesis by targeting JMJD8 in CRC. We also verified that miR-873-5p over-expression could suppress CRC cell growth by inhibiting JMJD8 and its downstream NF-kappa B pathway in CRC. Hence, miR-873-5p inhibited tumour growth, and it may be a potential biomarker and a promising treatment for CRC.