Journal article
miR-301a expression: Diagnostic and prognostic marker for prostate cancer
Urologic oncology, Vol.36(11), pp.503.e9-503.e15
11/2018
DOI: 10.1016/j.urolonc.2018.07.014
PMID: 30195463
Abstract
•miR-301a expression is higher in serum and tissue and correlates with increased Gleason score.•RUNX3 has been identified as a target for miR-301a and activates Rho signaling in prostate cancer.•Combining miR-301a with PSA values may help to stratify risk in patients and improve biopsy candidacy
Prostate-specific antigen screening for prostate cancer (CaP) remains controversial. This study establishes the role of microRNA 301a (miR-301a) as a supplemental biomarker that can distinguish between patients with benign prostate hyperplasia and clinically significant CaP. We evaluate the ability of miR-301a to predict the adverse pathology of CaP.
In the first cohort, serum and prostate tumor samples were obtained from thirteen patients with Benign prostate hyperplasia (BPH), twelve patients with Gleason 6, and sixteen patients with Gleason 7 prostate adenocarcinoma. In the second cohort, 40 prostatectomy cases were selected (BPH:12, Gleason 6:12 and Gleason 7:16). MiRNA was extracted from serum and tumor samples. Quantitative reverse transcription-polymerase chain reaction was performed for detection of miR-301a. To understand the molecular role of miR-301a, we performed cell viability, Western blots, promoter analysis, overexpression, and silencing studies in BPH and DU-145 cell lines.
MiR-301a demonstrated a significantly higher expression in both serum and tumor tissue in patients with CaP when compared to patients with BPH (P = 0.011 and 0.013 for serum and tissue expression, respectively). Expression of miR-301a in prostatectomy specimens correlated with increased Gleason score. We demonstrated that miR-301a inhibited the pro-apoptotic function of RUNX3, and activated ROCK1-mediated pro-survival signal in CaP. Silencing miR-301a initiated the pro-apoptotic function of RUNX3 by inhibiting ROCK1 expression in CaP cells.
Expression of miR-301a could be a valuable adjunct tool for stratifying patients with elevated prostate-specific antigen, as well as those diagnosed with CaP. Including the miR-301a as an additional variable in MSKCC post-prostatectomy nomogram improved its ability in facilitating clinical decision-making.
Details
- Title: Subtitle
- miR-301a expression: Diagnostic and prognostic marker for prostate cancer
- Creators
- Venkatesh Kolluru - University of LouisvilleBalaji Chandrasekaran - University of LouisvilleAshish Tyagi - University of LouisvilleAdnan Dervishi - University of LouisvilleMurali Ankem - University of LouisvilleXiaofang Yan - University of LouisvilleKong Maiying - University of LouisvilleHouda Alatassi - University of LouisvilleSaad P. Shaheen - VAMC, Pathology & Lab Medicine, Louisville, KY.Jamie C Messer - University of LouisvilleAngelena Edwards - University of LouisvilleAhmed Haddad - University of LouisvilleChendil Damodaran - University of Louisville
- Resource Type
- Journal article
- Publication Details
- Urologic oncology, Vol.36(11), pp.503.e9-503.e15
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.urolonc.2018.07.014
- PMID
- 30195463
- ISSN
- 1078-1439
- eISSN
- 1873-2496
- Language
- English
- Date published
- 11/2018
- Academic Unit
- Stead Family Department of Pediatrics; Urology
- Record Identifier
- 9984319980202771
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