MicroRNA‑139‑5p regulates chronic inflammation by suppressing nuclear factor‑κB activity to inhibit cell proliferation and invasion in colorectal cancer

Abstract

The inflammatory microenvironment, which mediates the initiation and malignant development of tumors, has been reported to be associated with microRNA (miRNA) dysregulation. In the present study, the expression of miR-139-5p was analyzed in colorectal cancer (CRC) cell lines SW480, HT29, HCT-8, LoVo and HCT116, aiming to investigate the function and mechanism of miR-139-5p in the regulation of the malignant phenotypes of CRC. miR-139-5p expression was found to be considerably downregulated in CRC cell lines compared with the human normal colon mucosal epithelial cell line NCM460. Subsequently, it was demonstrated that overexpression of miR-139-5p in colon cancer cell lines significantly suppressed the cell proliferation in vitro and in vivo. In addition, overexpression of miR-139-5p further inhibited the invasion ability of colon cancer cells in vitro, concomitantly with downregulation of key invasion-associated proteins, including matrix metalloproteinase 9 (MMP9) and MMP7. Furthermore, it was demonstrated that overexpression of miR-139-5p decreased the expression levels of inflammatory cytokines, including interleukin-1beta (IL-1beta), IL-6 and tumor necrosis factor-alpha (TNF-alpha), by suppressing nuclear factor (NF)-kappaB activity. Therefore, these findings collectively indicated that miR-139-5p regulated chronic inflammation by suppressing NF-kappaB activity in order to inhibit cell proliferation and invasion in CRC, thereby indicating a novel molecular mechanism in CRC therapy.