Enwald Max, Lehtimäki Terho, Mishra Pashupati P, Mononen Nina, Murtola Teemu J, Raitoharju Emma
Pirkanmaa Hospital District, Fimlab Laboratories, and Finnish Cardiovascular Research Center Tampere, Department of Clinical Chemistry, Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland.
Faculty of Medicine and Health Technology, Tampere University, 33520 Tampere, Finland.
Cancers (Basel). 2021 Jul 15;13(14):3537. doi: 10.3390/cancers13143537.
MicroRNAs are important in prostate cancer development, progression and metastasis. The aim of this study was to test microRNA expression profile in prostate tissue obtained from prostate cancer patients for associations with various prostate cancer related factors and to pinpoint the predicted target pathways for these microRNAs. Prostate tissue samples were obtained at prostatectomy from patients participating in a trial evaluating impact of pre-operative atorvastatin on serum prostate specific antigen (PSA) and Ki-67 expression in prostate tissue. Prostate tissue microRNA expression profiles were analyzed using OpenArray MicroRNA Panel. Pathway enrichment analyses were conducted for predicted target genes of microRNAs that correlated significantly with studied factors. Eight microRNAs correlated significantly with studied factors of patients after Bonferroni multiple testing correction. MiR-485-3p correlated with serum HDL-cholesterol levels. In atorvastatin-treated subjects, miR-34c-5p correlated with a change in serum PSA and miR-138-3p with a change in total cholesterol. In the placebo arm, both miR-576-3p and miR-550-3p correlated with HDL-cholesterol and miR-627 with PSA. In pathway analysis, these eight microRNAs related significantly to several pathways relevant to prostate cancer. This study brings new evidence from the expression of prostate tissue microRNAs and related pathways that may link risk factors to prostate cancer and pinpoint new therapeutic possibilities.
微小RNA在前列腺癌的发生、发展和转移过程中起着重要作用。本研究旨在检测前列腺癌患者前列腺组织中的微小RNA表达谱,以探寻其与各种前列腺癌相关因素的关联,并明确这些微小RNA的预测靶标途径。前列腺组织样本取自参与一项试验的患者,该试验旨在评估术前阿托伐他汀对血清前列腺特异性抗原(PSA)及前列腺组织中Ki-67表达的影响。采用开放式微阵列微小RNA分析板对前列腺组织微小RNA表达谱进行分析。对与研究因素显著相关的微小RNA的预测靶基因进行通路富集分析。经过Bonferroni多重检验校正后,有8种微小RNA与患者的研究因素显著相关。MiR-485-3p与血清高密度脂蛋白胆固醇水平相关。在阿托伐他汀治疗的受试者中,miR-34c-5p与血清PSA的变化相关,miR-138-3p与总胆固醇的变化相关。在安慰剂组中,miR-576-3p和miR-550-3p均与高密度脂蛋白胆固醇相关,miR-627与PSA相关。在通路分析中,这8种微小RNA与几条与前列腺癌相关的通路显著相关。本研究从前列腺组织微小RNA的表达及相关通路中获得了新证据,这些证据可能将危险因素与前列腺癌联系起来,并确定新的治疗可能性。