MicroRNA-301a promotes migration and invasion by targeting TGFBR2 in human colorectal cancer

Journal of Experimental & Clinical Cancer Research

Mingliang Wang³  Minhua Zheng²  Lu Zang²  Bo Feng²  Jin Hu²  Hongchao Zhao¹  Runsen Jin²  Tao Zhang²  Wenpeng Zhang² 

[1] Department of General Surgery, the First Affiliated Hospital of Zhengzhou University, ᅟ, Zhengzhou 450052 Henan Province, China;ᅟ, Shanghai Minimally Invasive Surgery Center, Shanghai 200025, P.R. China;Department of General Surgery, Luwan Branch of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200020, P.R. China

关键词: TGFBR2;    Invasion;    Metastasis;    miRNA-301a;    CRC;   

Others  :  1135983
DOI  :  10.1186/s13046-014-0113-6

 received in 2014-09-17, accepted in 2014-12-15,  发布年份 2014

【 摘 要 】

Background

MicroRNAs (miRNAs) have been reported to play crucial roles in regulating a variety of genes pivotal for tumor metastasis. MicroRNA-301a (miR-301a) is overexpressed and displays oncogenic activity in many cancers. However, little is known about the potential roles of miR-301a in colorectal cancer (CRC).

Methods

Taqman probe stem-loop real-time PCR was used to quantitatively measure the expression level of miR-301a in 48 cases of CRC tissues and the matched adjacent non-tumor mucosa as well as in CRC cell lines. miR-301a mimics and inhibitors were used to up-regulate and down-regulate miR-301a in CRC cells, respectively; lentivirus was used to construct miR-301a stably up- and down-regulated CRC cell lines. Metastasis ability was evaluated by transwell and wound healing assays while invasion was measured by transwell coated with matrix gel in vitro; in vivo metastasis was performed on nude mice model. The target of miR-301a was predicted by TargetScan software and validated by qRT-PCR, immunohistochemistry, western blot and luciferase reporter gene assay.

Results

The expression of miR-301a was significantly higher in lymph node metastasis positive CRC samples compared with negative ones. Downregulation of miR-301a significantly inhibited the migration and invasion both in vitro and in vivo while forced up-regulation of miR-301a promoted migration and invasion. TGFBR2 was identified to be the downstream target of miR-301a. Knockdown of TGFBR2 in cells treated by miR-301a inhibitor elevated the previously abrogated migration and invasion.

Conclusions

Our data indicated that miR-301a correlated with the metastatic and invasive ability in human colorectal cancers and miR-301a exerted its role as oncogene by targeting TGFBR2.

【 授权许可】

   
2014 Zhang et al.; licensee BioMed Central.

【 图 表 】

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