MicroRNA-1/206 targets c-Met and inhibits rhabdomyosarcoma development.
MicroRNAs (miRNAs) are endogenous short (approximately 22) nucleotide RNAs that regulate gene function by modification of target mRNAs. miRNA-1 (miR-1) and miRNA-206 (miR-206) are highly expressed in skeletal muscle. Due to the tissue-specific nature of miR-1/206 for skeletal muscles, we investigated the role of miR-1/206 in the development of rhabdomyosarcoma. Initially, we demonstrated that miR-1/206 expression was suppressed in rhabdomyosarcomas and found at very low levels in a rhabdomyosarcoma RD cell line. Transient transfection of miR-1/206 into cultured RD cells led to a significant decrease in cell growth and migration. Using bioinformatics, we identified two putative miR-1/206 binding sites within the 3'-untranslated region of the human c-Met mRNA. miR-1/206 was then shown to have activity on mRNA expression by targeting the c-Met 3'-untranslated region. The expression of c-Met protein was shown to be down-regulated by subsequent Western blot analysis. Conversely, up-regulation of c-Met was confirmed in tissue samples of human rhabdomyosarcoma, with its level inversely correlated with miR-1/206 expression. In vivo, miR-1/206-expressing tumor cells showed growth delay in comparison with negative control. Our results demonstrated that miR-1/206 suppressed c-Met expression in rhabdomyosarcoma and could function as a potent tumor suppressor in c-Met-overexpressing tumors. Inhibition of miR-1/206 function could contribute to aberrant cell proliferation and migration, leading to rhabdomyosarcoma development.
Yan
Dongsheng
D
School of Ophthalmology and Optometry, Eye Hospital, Wenzhou Medical College, Wenzhou, Zhejiang 325003, China.
Dong
Xiang Da Eric
Xda E
Chen
Xiaoyan
X
Wang
Lihua
L
Lu
Chunjing
C
Wang
Jiao
J
Qu
Jia
J
Tu
Lili
L
D020413:3' Untranslated Regions / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D018482:Muscle, Skeletal / Q000378:metabolism; D009368:Neoplasm Transplantation; D009928:Organ Specificity; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis*; D012208:Rhabdomyosarcoma / Q000378:metabolism*; D014162:Transfection; D014183:Transplantation, Heterologous
D020413:3' Untranslated Regions; C544547:MIRN1 microRNA, human; D035683:MicroRNAs; D019859:Proto-Oncogene Proteins c-met