Expression of miR-27a-3p is an independent predictive factor for recurrence in clear cell renal cell carcinoma

Oncotarget. 2015 Aug 28;6(25):21645-54. doi: 10.18632/oncotarget.4064.

Abstract

MicroRNAs (miRNAs) are noncoding RNAs that regulate gene expression and function in tumor development and progression. We previously identified up-regulated miRNAs in clear cell renal cell carcinoma (ccRCC) compared to matched-pair normal kidney by microarray. Here, we identify miRNAs that are up-regulated in ccRCC and are also correlated with survival and/or recurrence. Twenty-four samples from ccRCC patients who underwent nephrectomies between 2011 and 2012 were divided into two groups: one of eleven patients who experienced recurrence (Group 1), and one of thirteen patients with no evidence of disease (Group 2) 2 years after surgery. Analyzing 22 miRNAs that were up-regulated in ccRCC in our previous study, we identify five miRNAs that were statistically up-regulated in Group 1 versus Group 2 by quantitative real-time PCR. We then evaluated these miRNAs in an independent cohort of 159 frozen ccRCC samples. High levels of miR-27a-3p (p < 0.01) correlated with a worse progression-free survival rate. Multivariate analysis revealed that miR-27a-3p was an independent predictive factor for recurrence. For functional analysis, miR-27a-3p controlled cell proliferation, migration and invasion in RCC cell lines. MiR-27a-3p could act as oncogenic miRNA and may be a candidate for targeted molecular therapy in ccRCC.

Keywords: clear cell carcinoma; microRNA; prognosis; recurrence; renal cell carcinoma.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Renal Cell / genetics*
  • Cell Line, Tumor
  • Cohort Studies
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kidney / metabolism
  • Kidney Neoplasms / genetics*
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local
  • Oligonucleotide Array Sequence Analysis
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Real-Time Polymerase Chain Reaction

Substances

  • MIRN27 microRNA, human
  • MicroRNAs