MicroRNA-301a promotes migration and invasion by targeting TGFBR2 in human colorectal cancer
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  • 作者:Wenpeng Zhang (1) (2)
    Tao Zhang (1) (2)
    Runsen Jin (1) (2)
    Hongchao Zhao (4)
    Jin Hu (1) (2)
    Bo Feng (1) (2)
    Lu Zang (1) (2)
    Minhua Zheng (1) (2)
    Mingliang Wang (1) (2) (3)

    1. Department of General Surgery
    ; Ruijin Hospital ; Shanghai Jiao Tong University School of Medicine ; Shanghai ; 200025 ; P.R. China
    2. 釁? Shanghai Minimally Invasive Surgery Center
    ; Shanghai ; 200025 ; P.R. China
    4. Department of General Surgery
    ; the First Affiliated Hospital of Zhengzhou University ; 釁? Zhengzhou ; 450052 Henan Province ; China
    3. Department of General Surgery
    ; Luwan Branch of Ruijin Hospital ; Shanghai Jiao Tong University School of Medicine ; Shanghai ; 200020 ; P.R. China
  • 关键词:CRC ; miRNA ; 301a ; Metastasis ; Invasion ; TGFBR2
  • 刊名:Journal of Experimental & Clinical Cancer Research
  • 出版年:2014
  • 出版时间:December 2014
  • 年:2014
  • 卷:33
  • 期:1
  • 全文大小:1,941 KB
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  • 刊物主题:Oncology; Cancer Research;
  • 出版者:BioMed Central
  • ISSN:1756-9966
文摘
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.

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