MicroRNA-1 and microRNA-499 downregulate the expression of the ets1             proto-oncogene in HepG2 cells.
MicroRNAs may function to promote or suppress tumor development, depending             on the cellular context. The important role of microRNAs in regulating molecular             pathways underlying tumorigenesis has been emphasized in hepatocellular carcinoma             (HCC). MicroRNAs regulate gene expression via post-transcriptional mechanisms             by inhibiting translation or by degrading mRNA. In this study, we show that microRNA-1             (miR-1) and microRNA-499 (miR-499) are capable of repressing the expression of             the ets1 proto-oncogene, which plays a fundamental role in the extracellular matrix             (ECM) degradation, a process required for tumor cell invasion and migration. We             used luciferase reporter assays to demonstrate that miR-1 and miR-499 target the             3' untranslated region (UTR) of ets1. Overexpression of miR-1 and miR-499 in HepG2 cells             led to downregulation of ets1 mRNA and protein as assessed by quantitative reverse             transcription PCR and western blot analysis. Furthermore, overexpression of miR-1             and miR-499 inhibited the invasion and migration of HepG2 cells in matrigel invasion             and transwell migration assays, respectively. These results suggest that miR-1             and miR-499 may play an important role in the pathogenesis of HCC by regulating             ets1.
Beijing Institute of Radiation Medicine, Beijing, PR China.
Wei
W
Wei
Zheng
Z
Hu
Hanjing
H
Fu
Yi
Y
Tie
Haihong
H
Zhang
Yongge
Y
Wu
Xiaofei
X
Zheng
D020413:3' Untranslated Regions; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1 / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection
D020413:3' Untranslated Regions; C494041:ETS1 protein, human; C000715470:MAS1 protein, human; C544547:MIRN1 microRNA, human; C548683:MIRN499 microRNA, human; D035683:MicroRNAs; D000090063:Proto-Oncogene Mas; D050784:Proto-Oncogene Protein c-ets-1; D012333:RNA, Messenger; D034741:RNA, Small Interfering