Effects of miR-34a on cell growth and chemoresistance in prostate cancer PC3 cells.
Tumor suppressor p53 transcriptionally regulates expression of microRNA-34a, which confers translational inhibition and mRNA degradation of genes involved in cell cycle control and apoptosis. In various cancers, miR-34a expression is lost or reduced. Here, we investigated the role of miR-34a in prostate cancer cell lines. MiR-34a expression was markedly reduced in p53-null PC3 cells and p53-mutated DU145 cells compared with LNCaP cells expressing wild-type p53. In PC3 cell, ectopic expression of miR-34a decreased the SIRT1 mRNA and protein levels as well as protein levels of known direct target genes. Reporter assays revealed that miR-34a-induced SIRT1 inhibition occurred at the transcriptional but not post-transcriptional level despite the presence of a potential miR-34a binding site within its 3'-UTR. Ectopic miR-34a expression resulted in cell cycle arrest and growth inhibition and attenuated chemoresistance to anticancer drug camptothecin by inducing apoptosis, suggesting a potential role of miR-34a for the treatment of p53-defective prostate cancer.
Fujita
Yasunori
Y
Department of Longevity and Aging Research, Gifu International Institute of Biotechnology, Kakamigahara, Gifu, Japan.
Kojima
Keitaro
K
Hamada
Nanako
N
Ohhashi
Riyako
R
Akao
Yukihiro
Y
Nozawa
Yoshinori
Y
Deguchi
Takashi
T
Ito
Masafumi
M
D020413:3' Untranslated Regions / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001665:Binding Sites; D002166:Camptothecin / Q000494:pharmacology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D056564:Sirtuin 1; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D059004:Topoisomerase I Inhibitors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D020413:3' Untranslated Regions; D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D059004:Topoisomerase I Inhibitors; D016159:Tumor Suppressor Protein p53; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins; D002166:Camptothecin