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Functional roles and potential clinical application of miRNA‐345‐5p in prostate cancer
Author(s) -
Tinay Ilker,
Tan Mingyue,
Gui Bin,
Werner Lillian,
Kibel Adam S.,
Jia Li
Publication year - 2018
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23650
Subject(s) - prostate cancer , microrna , prostate , medicine , cancer , prostate disease , oncology , pathology , biology , genetics , gene
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.