MicroRNA-539 inhibits colorectal cancer progression by directly targeting SOX4.

Abstract

Colorectal cancer (CRC) is the third most prevalent cancer and the fourth most common cause of cancer-associated mortality in males and females globally. Aberrant expression of microRNA-539 (miR-539) has been reported in multiple types of cancer. However, miR-539 expression, function and underlying mechanisms have not been clearly elucidated in CRC. In the present study, miR-539 expression was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in CRC tissues and cell lines. The effects of miR-539 on CRC cells were further examined in in vitro studies. In addition, the direct targets of miR-539 in CRC were investigated using bioinformatics, luciferase reporter assays, RT-qPCR and western blotting. miR-539 was revealed to be significantly downregulated in CRC cell lines and tissues. Decreased miR-539 expression was associated with lymph node metastasis and tumor-node-metastasis stage in patients with CRC. Functional assays revealed that the rescue of miR-539 expression attenuated CRC cell proliferation and invasion in vitro. Additionally, SRY-box 4 (SOX4) was validated as a direct target gene of miR-539 in CRC. Furthermore, SOX4 was revealed to be upregulated in CRC tissues at the mRNA and protein level. A significant negative correlation between miR-539 and SOX4 mRNA expression levels was observed in CRC tissues. Furthermore, upregulation of SOX4 partially restored the tumor suppressive effects of miR-539 on CRC cell proliferation and invasion. Taken together, this suggests that miR-539 may serve tumor-suppressive functions in CRC during the process of malignant transformation, by directly targeting SOX4. miR-539/SOX4-based targeted therapy may represent a potential novel treatment for patients with CRC.