MiR-1247-5p is overexpressed in castration resistant prostate cancer and targets MYCBP2.
BACKGROUND
Recently, there has been increasing attention on the role of microRNAs (miRNAs) in cancer development. Several expression profiling studies have provided evidence of aberrant expression of miRNAs in prostate cancer and have highlighted the potential use of specific miRNA expression signatures as prognostic or predictive markers. Here we report an expression analysis of miR-1247-5p, miR-1249, miR-1269a, miR-1271-5p, miR-1290, miR-1291, and miR-1299.


METHODS
qRT-PCR was performed to validate the differential expression of miRNAs in clinical samples, and the effect of miR-1247-5p was studied in prostate cancer cell lines transiently transfected with a miR-1247-5p mimic. The expression of miR-1247-5p's putative target MYCBP2 was evaluated by qRT-PCR and Western blotting, and the interaction of the miRNA with the target gene was assessed using a luciferase assay.


RESULTS
We found a significant up-regulation of miR-1247-5p in castration-resistant prostate cancer (CRPC) samples compared to non-malignant prostate. The expression of miR-1247-5p was subsequently studied in prostate cancer (PC) cell lines where an up-regulation of miR-1247-5p was observed in the androgen-independent PC-3 model. Target prediction analysis for miR-1247-5p performed online revealed that MYCBP2 (myc-binding protein 2) was a high-scoring potential target. Functional studies in vitro performed using PC-3 and LNCaP models confirmed the down-regulation of MYCBP2 at the mRNA and protein levels, and a luciferase assay showed interaction between the miRNA and target gene.


CONCLUSIONS
miR-1247-5p is overexpressed in CRPC and targets MYCBP2.
Prostate Cancer Research Center, Institute of Biosciences and Medical Technology-BioMediTech and Fimlab Laboratories, University of Tampere and Tampere University Hospital, Tampere, Finland.
Mauro
M
Scaravilli
Kati P
KP
Porkka
Anniina
A
Brofeldt
Matti
M
Annala
Teuvo L J
TL
Tammela
Guido W
GW
Jenster
Matti
M
Nykter
Tapio
T
Visakorpi
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000368:Aged; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis*; D008875:Middle Aged; D064129:Prostatic Neoplasms, Castration-Resistant / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D035683:MicroRNAs; D012333:RNA, Messenger; C114022:MYCBP2 protein, human; D044767:Ubiquitin-Protein Ligases
MYCBP2; castration resistant prostate cancer; microRNA