miR-133b regulates the MET proto-oncogene and inhibits the growth of colorectal cancer cells in vitro and in vivo.
Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. MicroRNAs (miRs) are single-stranded, noncoding RNAs that are important in many biological processes. Although the oncogenic and tumor-suppressive functions of several miRs have been characterized, their precise biological roles remain largely unexplored. In the present study, the role of miR-133b was identified in the regulation of CRC cell proliferation and apoptosis. miR-133b expression was shown to be greatly downregulated in human CRC cells compared to normal colon cells. Downregulation of miR-133b expression was also significant in six of eight human CRC tissues compared with adjacent normal tissues. In the CRC cell lines SW-620 and HT-29, ectopic expression of miR-133b potently affected tumor cell proliferation and apoptosis in vitro and in vivo by direct targeting of the receptor tyrosine kinase MET. Transfection of SW-620 and HT-29 cells with miR-133b significantly suppressed a luciferase-reporter containing the MET-3'-untranslated region. Taken together, these results provide evidence that miR-133b regulated tumor cell proliferation and apoptosis through modulation of the MET signaling pathway.
Hu
Gui
G
Department of General Surgery, The Third Affiliated XiangYa Hospital of Central South University, Changsha, Hunan Province, China.
Chen
Daojin
D
Li
Xiaorong
X
Yang
Kaiyan
K
Wang
Hongxian
H
Wu
Wei
W
D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics; D017978:Receptors, Growth Factor / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D018709:Statistics, Nonparametric; D047368:Tumor Burden; D014407:Tumor Cells, Cultured
C000715470:MAS1 protein, human; C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D000090063:Proto-Oncogene Mas; D012334:RNA, Neoplasm; D017978:Receptors, Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met