MicroRNA‑539 inhibits colorectal cancer progression by directly targeting SOX4

Zhao,Jian; Xu,Jian; Zhang,Rui

doi:10.3892/ol.2018.8892

MicroRNA‑539 inhibits colorectal cancer progression by directly targeting SOX4

Authors:
- Jian Zhao
- Jian Xu
- Rui Zhang
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Affiliations: Department of Colorectal Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China
Published online on: June 4, 2018 https://doi.org/10.3892/ol.2018.8892
Pages: 2693-2700

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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.

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