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- Title
Role of miR-143 targeting KRAS in colorectal tumorigenesis.
- Authors
Chen, X; Guo, X; Zhang, H; Xiang, Y; Chen, J; Yin, Y; Cai, X; Wang, K; Wang, G; Ba, Y; Zhu, L; Wang, J; Yang, R; Zhang, Y; Ren, Z; Zen, K; Zhang, J; Zhang, C-Y
- Abstract
Dysregulated expression of microRNAs (miRNAs) is associated with a variety of diseases, including colorectal cancer. By comparing more than 200 miRNAs in 13 pairs of matched colorectal cancer and normal adjacent tissue samples through qRT-PCR and microarray analysis, we found a widespread disruption of miRNA expression during colorectal tumorigenesis. In particular, among a panel of presumed targets generated by in silico analysis that may interact with these aberrantly expressed miRNAs, KRAS oncogene has been further experimentally validated as the target of miR-143. First, an inverse correlation between KRAS protein and miR-143 in vivo was found. Second, KRAS expression in Lovo cells was significantly abolished by treatment with miR-143 mimic, whereas miR-143 inhibitor increased KRAS protein level. Third, luciferase reporter assay confirmed that miR-143 directly recognize the 3'-untranslated region of KRAS transcripts. Four, Lovo cells treated with miR-143 inhibitor showed a stimulated cell proliferation, whereas miR-143 overexpression had an opposite effect. Finally, inhibition of KRAS expression by miR-143 inhibits constitutive phosphorylation of ERK1/2. Taken together, the present study provides the first evidences that miR-143 is significant in suppressing colorectal cancer cell growth through inhibition of KRAS translation.
- Publication
Oncogene, 2009, Vol 28, Issue 10, p1385
- ISSN
1476-5594
- Publication type
Journal Article
- DOI
10.1038/onc.2008.474