MicroRNA-129 inhibits colorectal cancer cell proliferation, invasion and epithelial-to-mesenchymal transition by targeting SOX4

Abstract

Colorectal cancer (CRC) is one of the most common digestive tract cancers and ~90% of CRC-related deaths are caused by metastasis. MicroRNA (miR)-129 has been reported to be involved in the metastasis of various malignant tumors. However, the role of miR-129 in CRC metastasis remains unclear. The purpose of the present study was to identify the potential functions and mechanisms of action of miR-129 in CRC progression. The expression of miR-129 and sex-deter- mining region Y-related high-mobility group-box 4 (SOX4) was determined in CRC tissues or cell lines by reverse transcrip- tion-quantitative PCR, western blot or immunofluorescence assays. The mechanism underlying the role of miR-129 in CRC progression was assessed by MTT, wound healing, Transwell, western blot and dual-luciferase report assays. The results revealed that miR-129 was significantly decreased, whereas SOX4 was increased, in CRC tissues and cell lines. SW620 and SW480 cells exhibited a higher proliferation, migration and invasion capacity compared with NCM460 cells. miR-129 overexpression significantly inhibited cell proliferation, migra- tion, invasion and epithelial-to-mesenchymal transition (EMT), and it activated the nuclear factor (NF)-κB signaling pathway in CRC cells, while the inhibition of miR-129 exerted opposite effects. Additionally, SOX4 was identified as a direct target gene of miR-129. Taken together, the findings of the present study suggested that miR-129 may act as a tumor suppressor in CRC by inhibiting CRC cell proliferation, migration, invasion and EMT, in part through targeting the 3'-untranslated region of SOX4 mRNA, and the mechanism may involve activation of the NF-κB signaling pathway.