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- Title
MicroRNA-34a inhibits migration and invasion of colon cancer cells via targeting to Fra-1.
- Authors
Wu, Jianmin; Wu, Gang; Lv, Lu; Ren, Yong-Feng; Zhang, Xue-Jiao; Xue, Yong-Feng; Li, Guiling; Lu, Xincheng; Sun, ZhongSheng; Tang, Kai-Fu
- Abstract
MicroRNA-34a (miR-34a), a transcriptional target of p53, is a well-known tumor suppressor gene. Here, we identified Fra-1 as a new target of miR-34a and demonstrated that miR-34a inhibits Fra-1 expression at both protein and messenger RNA levels. In addition, we found that p53 indirectly regulates Fra-1 expression via a miR-34a-dependant manner in colon cancer cells. Overexpression of miR-34a strongly inhibited colon cancer cell migration and invasion, which can be partially rescued by forced expression of the Fra-1 transcript lacking the 3′-untranslated region. The expression of matrix metalloproteinase (MMP)-1 and MMP-9, two enzymes involved in cell migration and invasion, was decreased in miR-34a-transfected cells, and this can be rescued by Fra-1 overexpression. Moreover, we found that miR-34a was downregulated in 25 of 40 (62.5%) colon cancer tissues, as compared with the adjacent normal colon tissues and that the expression of miR-34a was correlated with the DNA-binding activity of p53. Unexpectedly, the DNA-binding activity of p53 was not inversely correlated with Fra-1 expression, and a significant statistical inverse correlation between miR-34a and Fra-1 expression was only observed in 14 of 40 (35%) colon cancer tissues. Taken together, our in vitro data suggest that p53 regulates Fra-1 expression, and eventually cell migration/invasion, via a miR-34a-dependent manner. However, in vivo data indicate that the p53-miR-34a pathway is not the major regulator of Fra-1 expression in human colon cancer tissues.
- Subjects
MICRORNA; COLON cancer; CANCER cells; CELL migration; CANCER invasiveness; GENETIC transcription; GENE targeting; TUMOR suppressor genes
- Publication
Carcinogenesis, 2012, Vol 33, Issue 3, p519
- ISSN
0143-3334
- Publication type
Article
- DOI
10.1093/carcin/bgr304