期刊
INTERNATIONAL JOURNAL OF ONCOLOGY
卷 48, 期 5, 页码 2135-2143出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/ijo.2016.3430
关键词
colorectal cancer; transmembrane-4-L6 family 1; miR-9; invasion; metastasis
类别
资金
- Ministry of Health, Welfare and Family Affairs
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT, and the Future Planning [NRF-2015R1D1A3A01016026]
- Research Institute of Clinical Medicine of Chonbuk National University Hospital-Biomedical Research Institute of Chonbuk National University Hospital
Transmembrane-4-L6 family 1 (TM4SF1) is upregulated in colorectal carcinoma (CRC). However, the mechanism leading to inhibition of the TM4SF1 is not known. In the present study, we investigated the regulation of TM4SF1 and function of microRNAs (miRNAs) in CRC invasion and metastasis. We analyzed 60 colon cancers and paired normal specimens for TM4SF1 and miRNA-9 (miR-9) expression using quantitative real-time PCR. A bioinformatics analysis identified a putative miR-9 binding site within the 3'-UTR of TM4SF1. We also found that TM4SF1 was upregulated in CRC tissues and CRC cell lines. The expression of TM4SF1 was positively correlated with clinical advanced stage and lymph node metastasis. Moreover, a luciferase assay revealed that miR-9 directly targeted 3'-UTR-TM4SF1. Overexpression of miR-9 inhibited expression of TM4SF1 mRNA and protein, wound healing, transwell migration and invasion of SW480 cells, whereas, overexpression of anti-miR-9 and siRNA-TM4SF1 inversely regulated the TM4SF1 mRNA and protein level in HCT116 cells. Furthermore, miR-9 suppressed not only TM4SF1 expression but also MMP-2, MMP-9 and VEGF expression. In clinical specimens, miR-9 was generally downregulated in CRC and inversely correlated with TM4SF1 expression. These results suggest that miR-9 functions as a tumor-suppressor in CRC, and that its suppressive effects mediate invasion and metastasis by inhibition of TM4SF1 expression. Our results also indicate that miR-9 might be a novel target for the treatment of CRC invasion and metastasis.
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