title: Role of miR-143 targeting KRAS in colorectal tumorigenesis.
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.
authors.affiliation: Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: X
authors.initials: X
authors.lastname: Guo
authors.forename: H
authors.initials: H
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Xiang
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: Y
authors.initials: Y
authors.lastname: Yin
authors.forename: X
authors.initials: X
authors.lastname: Cai
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Ba
authors.forename: L
authors.initials: L
authors.lastname: Zhu
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.forename: R
authors.initials: R
authors.lastname: Yang
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: Z
authors.initials: Z
authors.lastname: Ren
authors.forename: K
authors.initials: K
authors.lastname: Zen
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: C-Y
authors.initials: CY
authors.lastname: Zhang
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics / Q000517:prevention & control*; D016147:Genes, Tumor Suppressor; D006801:Humans; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D016283:Proto-Oncogene Proteins p21(ras); D020133:Reverse Transcriptase Polymerase Chain Reaction; D018631:ras Proteins / Q000037:antagonists & inhibitors*
chemical_list: C117307:KRAS protein, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins