miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate cell growth by repressing its target CAND1 expression.
Recent advances in cancer biology reveal that microRNAs (miRNAs) are involved in the regulation of cancer-related genes, or they function as tumor suppressors or oncogenes. In prostate cancer, evidence has accumulated for the contribution of the androgen-dependent gene network to tumor growth, although the precise functions of miRNAs in prostate cancer remain to be investigated. Here, we identified androgen-responsive miRNAs by the short RNA sequencing analysis in LNCaP prostate cancer cells. Among 10 miRNAs with known sequences, we have determined that miR-148a reduces the expression of cullin-associated and neddylation-dissociated 1 (CAND1), a negative regulator of SKP1-Cullin1-F-box (SCF) ubiquitin ligases, by binding to the 3'-untranslated region of CAND1 mRNA. CAND1 knockdown by small interfering RNA promoted the proliferation of LNCaP cells. Our study indicates the potential contribution of miR-148a to the growth of human prostate cancer.
Murata
T
T
Department of Anti-Aging Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Takayama
K
K
Katayama
S
S
Urano
T
T
Horie-Inoue
K
K
Ikeda
K
K
Takahashi
S
S
Kawazu
C
C
Hasegawa
A
A
Ouchi
Y
Y
Homma
Y
Y
Hayashizaki
Y
Y
Inoue
S
S
D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000728:Androgens / Q000494:pharmacology; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D020413:3' Untranslated Regions; D000728:Androgens; C486317:CAND1 protein, human; C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D014157:Transcription Factors