c-Myc suppressed E-cadherin through miR-9 at the post-transcriptional level.
c-Myc oncoprotein is overexpressed in most human cancers and regulates different genes and pathways in different cell types. E-cadherin expression is repressed by MYC through a post-transcriptional mechanism, but the exact mechanism remains elusive. Since E-cadherin is a direct target of miR-9 and miR-9 can be activated by MYC and MYCN, this suggests that c-Myc negatively modulates E-cadherin through a microRNA pathway. We have established a c-Myc-inducible expression system in which the protein level and transcriptional activity of c-Myc is significantly upregulated upon doxycycline induction. Overexpressed c-Myc led to an EMT-like conversion in the T-REx-293 cells and resulted in a significant decrease in E-cadherin and an increase in Vimentin. Stem-loop RT-PCR showed elevated expression of miR-9 when c-Myc was induced to be overexpressed. Regarding the relationship of c-Myc, miR-9 and E-cadherin, the expression of miR-9 was curtailed by using antagomir-9 in induced overexpressing c-Myc. Restoration of E-cadherin expression became much stronger in the presence of c-Myc. Thus c-Myc represses E-cadherin at the post-transcriptional level through miR-9.
Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, Cancer Institute & Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, PR China.
Mei
M
Liu
Hongxia
H
Zhu
Shangbin
S
Yang
Zaozao
Z
Wang
Jinfeng
J
Bai
Ningzhi
N
Xu
D020413:3' Untranslated Regions; D015703:Antigens, CD; D001483:Base Sequence; D001665:Binding Sites; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000502:physiology*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D020413:3' Untranslated Regions; D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C541874:MIRN92 microRNA, human; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger