Role of miR-143 targeting KRAS in colorectal tumorigenesis.
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.
Chen
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X
Jiangsu Diabetes Center, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
Guo
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X
Zhang
H
H
Xiang
Y
Y
Chen
J
J
Yin
Y
Y
Cai
X
X
Wang
K
K
Wang
G
G
Ba
Y
Y
Zhu
L
L
Wang
J
J
Yang
R
R
Zhang
Y
Y
Ren
Z
Z
Zen
K
K
Zhang
J
J
Zhang
C-Y
CY
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*
C117307:KRAS protein, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins