Kolluru Venkatesh, Chandrasekaran Balaji, Tyagi Ashish, Dervishi Adnan, Ankem Murali, Yan Xiaofang, Maiying Kong, Alatassi Houda, Shaheen Saad P, C Messer Jamie, Edwards Angelena, Haddad Ahmed, Damodaran Chendil
Department of Urology, University of Louisville, Louisville, KY.
Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY.
Urol Oncol. 2018 Nov;36(11):503.e9-503.e15. doi: 10.1016/j.urolonc.2018.07.014. Epub 2018 Sep 5.
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.
前列腺癌（CaP）的前列腺特异性抗原筛查仍存在争议。本研究确定了微小RNA 301a（miR-301a）作为一种补充生物标志物的作用，其可区分良性前列腺增生患者和具有临床意义的CaP患者。我们评估了miR-301a预测CaP不良病理的能力。
在第一个队列中，从13例良性前列腺增生（BPH）患者、12例Gleason 6级患者和16例Gleason 7级前列腺腺癌患者中获取血清和前列腺肿瘤样本。在第二个队列中，选择了40例前列腺切除术病例（BPH：12例，Gleason 6级：12例，Gleason 7级：16例）。从血清和肿瘤样本中提取微小RNA。进行定量逆转录-聚合酶链反应以检测miR-301a。为了解miR-301a的分子作用，我们在BPH和DU-145细胞系中进行了细胞活力、蛋白质免疫印迹、启动子分析、过表达和沉默研究。
与BPH患者相比，CaP患者血清和肿瘤组织中miR-301a的表达均显著更高（血清和组织表达的P值分别为0.011和0.013）。前列腺切除标本中miR-301a的表达与Gleason评分增加相关。我们证明miR-301a抑制了RUNX3的促凋亡功能，并激活了CaP中ROCK1介导的促生存信号。在CaP细胞中沉默miR-301a通过抑制ROCK1表达启动了RUNX3的促凋亡功能。
miR-301a的表达可能是对前列腺特异性抗原升高患者以及被诊断为CaP的患者进行分层的有价值辅助工具。将miR-301a作为额外变量纳入MSKCC前列腺切除术后列线图可提高其辅助临床决策的能力。
