MicroRNA-330 acts as tumor suppressor and induces apoptosis of prostate cancer cells through E2F1-mediated suppression of Akt phosphorylation.
MicroRNAs (miRNAs) make up a novel class of gene regulators; they function as oncogenes or tumor suppressors by targeting tumor-suppressor genes or oncogenes. A recent study that analysed a large number of human cancer cell lines showed that miR-330 is a potential tumor-suppressor gene. However, the function and molecular mechanism of miR-330 in determining the aggressiveness of human prostate cancer has not been studied. Here, we show that miR-330 is significantly lower expressed in human prostate cancer cell lines than in nontumorigenic prostate epithelial cells. Bioinformatics analyses reveal a conserved target site for miR-330 in the 3'-untranslated region (UTR) of E2F1 at nucleotides 1018-1024. MiR-330 significantly suppressed the activity of a luciferase reporter containing the E2F1-3'-UTR in the cells. This activity could be abolished with the transfection of anti-miR-330 or mutated E2F1-3'-UTR. In addition, the expression level of miR-330 and E2F1 was inversely correlated in cell lines and prostate cancer specimens. After overexpressing of miR-330 in PC-3 cells, cell growth was suppressed by reducing E2F1-mediated Akt phosphorylation and thereby inducing apoptosis. Collectively, this is the first study to show that E2F1 is negatively regulated by miR-330 and also show that miR-330 induces apoptosis in prostate cancer cells through E2F1-mediated suppression of Akt phosphorylation.
Lee
K-H
KH
Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
Chen
Y-L
YL
Yeh
S-D
SD
Hsiao
M
M
Lin
J-T
JT
Goan
Y-G
YG
Lu
P-J
PJ
D020413:3' Untranslated Regions / Q000235:genetics; D017209:Apoptosis; D045744:Cell Line, Tumor; D002470:Cell Survival; D015536:Down-Regulation; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000502:physiology*; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
D020413:3' Untranslated Regions; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt