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

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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-1β (IL-1β), IL-6 and tumor necrosis factor-α (TNF-α), by suppressing nuclear factor (NF)-κB activity. Therefore, these findings collectively indicated that miR-139-5p regulated chronic inflammation by suppressing NF-κB activity in order to inhibit cell proliferation and invasion in CRC, thereby indicating a novel molecular mechanism in CRC therapy.