Background: MicroRNAs (miRNAs) are small non-coding RNAs, which negatively regulate gene expression and impact prostate cancer (PCa) growth and progression. Circulating miRNAs are stable and detectable in cell-free body fluids, such as serum. Investigation of circulating miRNAs presents great potential in uncovering new insights into the roles of miRNAs in PCa diagnosis and therapy.
Methods: Using TaqMan miRNA quantitative reverse transcription polymerase chain reaction (RT-qPCR), we compared the expression levels of five miRNAs (miR-193a-3p, miR-9-3p, miR-335-5p, miR-330-3p, and miR-345-5p) in serum samples from 20 normal individuals without cancer, 25 patients with localized disease, 25 patients with hormone-naïve or hormone sensitive metastatic disease, and 25 patients with metastatic castration-resistant prostate cancer (CRPC). These five miRNAs were identified as potential oncogenes in our previous studies. MiR-345-5p was further investigated for its functional roles in CRPC cells.
Results: We discovered that miR-9-3p, miR-330-3p-3p, and miR-345-5p were significantly overexpressed in serum from PCa patients when compared to serum from individuals without cancer. No differential expression patterns were observed between different disease categories. However, patients who were in remission after androgen deprivation therapy (ADT) appeared to have significantly lower miR-345-5p levels compared to the rest of the groups. We further demonstrated that miR-345-5p promotes CRPC cell growth and migration in vitro and validated that CDKN1A (the gene encoding p21) is the direct target of miR-345-5p.
Conclusions: Our results set the stage for a further investigation on the potential application of circulating miR-345-5p as a biomarker for PCa diagnosis and therapeutic response. The oncogenic roles of miR-345-5p through targeting CDKN1A render it a potential therapeutic target for PCa.
Keywords: CDKN1A; circulating microRNAs; miR-345-5p; prostate cancer.
© 2018 Wiley Periodicals, Inc.