miR-148a is an androgen-responsive microRNA that promotes LNCaP prostate cell growth by repressing its target CAND1 expression

Abstract

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 miR148a 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 0 -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.

TET2 repression by androgen hormone regulates global hydroxymethylation status and prostate cancer progression

“…In LNCaP cells, a total of 44 miRNAs were significantly induced by DHT (41.2-fold), including representative AR-regulated miRNAs such as miR-125b 24 , miR-21 (ref. 25) and miR-148a 26 , while 30 miRNAs were induced by DHT (41.2-fold) in BicR cells. The members of the miR-29 family and miR-22 were the most responsive to androgen treatment in BicR cells compared with parental LNCaP cells.…”

Androgen-regulated miR-32 targets BTG2 and is overexpressed in castration-resistant prostate cancer

“…Additionally, the level of BIM protein was not reduced in miR-32-transfected cells according to the western blot analysis (Supplementary Figure S4). Recently, miR-148a was shown to target CAND1 in PC cells (Murata et al, 2010). However, CAND1 mRNA was not reduced in the pre-miR-148a-transfected LNCaP cells (Supplementary Table S5).…”

Comparative microRNA Profiling of Prostate Carcinomas with Increasing Tumor Stage by Deep Sequencing

“…exhibited the regulation pattern of stage-specific increasing expression with a dramatic reduction of expression in lymph node metastasizing prostate carcinoma. We, furthermore, selected miRNAs miR-15a and miR-148a because the functional role of these miRNAs in primary prostate carcinoma cases is currently under discussion (18)(19)(20). The changes in the expression levels of let-7c, miR-15a, miR-20a, miR-143, miR-145, miR-148a, miR-200b, and miR-375 observed by sequencing were analyzed by Northern blot analysis of the pooled RNAs employed in the generation of the cDNA libraries for sequencing as shown in Supplementary Fig.…”

“…2 and 3). miRNAs are short, noncoding RNAs of approximately [19][20][21][22][23][24][25] nucleotides that bind preferentially to specific sequences in the 3 0 -untranslated region (3 0 UTR) of mRNAs, resulting in either translational repression or mRNA degradation. Interaction of the miRNAs with their mRNA target ultimately leads to reduced protein synthesis via association with the Argonaute (Ago-) containing RNAinduced silencing complex (for a review, see ref.…”