Downregulation of miR-129 in peripheral blood mononuclear cells is a diagnostic and prognostic biomarker in prostate cancer

Int J Clin Exp Pathol. 2015 Nov 1;8(11):14335-44. eCollection 2015.

Abstract

Objective: The present study was designed to explore the clinical values of microRNA-129 (miR-129) expression in peripheral blood mononuclear cells for prostate cancer patients and the role of miR-129 in the proliferation of prostate cancer.

Methods: The peripheral blood mononuclear cells were isolated form blood simple from 98 patients confirmed with prostate cancer and 56 matched healthy volunteers. Reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) was employed to determine the expression level of miR-129 in peripheral blood mononuclear cells. Cox proportional hazards regression models and Kaplan-Meier analysis were used to evaluate the association of miR-129 expression with clinical and pathological characteristics of prostate cancer patients. The effect of miR-129 on the proliferation of prostate cancer cells in vitro was also determined.

Results: Reverse transcription quantitative real-time polymerase chain reaction (qRT-PCR) results showed that the expression of miR-129 was dramatically down-regulated in peripheral blood mononuclear cells for prostate cancer patients in comparison with healthy controls (P<0.05). The decrease in miR-129 expression in peripheral blood mononuclear cells was significantly associated with aggressive clinical pathological features such as histological grade (P=0.010), high preoperative PSA level (P=0.002), pathological stage (P=0.011), high Gleason score (P=0.005), lymph node metastasis (P=0.002), angiolymphatic invasion (P=0.004), biochemical recurrence (P=0.001). The prostate cancer patients with a low miR-129 expression in peripheral blood mononuclear cells had an obviously shorter BCR-free survival compared with high miR-129 expression (P<0.001). The Cox multivariate analysis established that the miR-129 expression may be an independent prognostic factor for biochemical recurrence (BCR)-free survival prostate cancer patients (P=0.000). The results of in vitro CCK-8 assays, as well as proliferating cell nuclear antigen (PCNA) and phosphorylated histone-3 (P-H3) (markers of proliferation) indicated that miR-129 overexpression markedly retarded the proliferation of PC-3 and DU-145 cells.

Conclusions: Our results provide the first evidence that the miR-129 is significantly downregulated in prostate cancer patients and multivariate analysis confirmed that miR-129 is a novel independent prognostic factor for prostate cancer. Overexpression of miR-129 exerts tumor suppressive functions and abrogates prostate cancer growth.

Keywords: miR-129; peripheral blood mononuclear cells; prognosis; proliferation; prostate cancer.

MeSH terms

  • Adult
  • Aged
  • Area Under Curve
  • Biomarkers, Tumor / blood*
  • Biomarkers, Tumor / genetics
  • Case-Control Studies
  • Cell Line, Tumor
  • Cell Proliferation
  • Chi-Square Distribution
  • Disease-Free Survival
  • Down-Regulation
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kaplan-Meier Estimate
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Neoplasm Staging
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Prostatic Neoplasms / blood*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy
  • ROC Curve
  • Reverse Transcriptase Polymerase Chain Reaction
  • Risk Factors
  • Transfection

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • Mirn129 microRNA, human