Dysregulated microRNA-224/apelin axis associated with aggressive progression and poor prognosis in patients with prostate cancer

Hum Pathol. 2015 Feb;46(2):295-303. doi: 10.1016/j.humpath.2014.10.027. Epub 2014 Nov 26.

Abstract

Our previous study revealed that microRNA (miR)-224 down-regulation could promote tumor progression of prostate cancer (PCa) and might be associated with poor biochemical recurrence-free survival of patients with this malignancy. However, the underlying mechanisms of miR-224 have not been fully elucidated. In the current study, apelin (APLN) was identified as a target gene of miR-224. Forced expression of miR-224 inhibited PCa cell invasion and migration by suppressing the expression of APLN. In addition, the down-regulation of miR-224 was negatively correlated with the up-regulation of APLN mRNA in PCa tissues. Moreover, miR-224 down-regulation was significantly associated with advanced clinical stage (P = .027) and metastasis (P = .001), whereas APLN up-regulation more frequently occurred in PCa tissues with advanced pathologic stage (P = .003), metastasis (P < .001), and prostate-specific antigen failure (P = .001). Furthermore, patients with PCa in the miR-224-low/APLN-high group more frequently had shorter biochemical recurrence-free survival than those in groups with other expression patterns of the 2 molecules. Taken together, our data strongly confirmed for the first time that the dysregulated miR-224/APLN axis may be associated with tumorigenesis and aggressive progression of PCa. More importantly, miR-224 down-regulation and APLN up-regulation may synergistically predict biochemical recurrence-free survival in patients with PCa.

Keywords: Apelin; Biochemical recurrence–free survival; Clinicopathological characteristic; MicroRNA-224; Prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apelin
  • Biomarkers, Tumor / metabolism*
  • Disease Progression
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Prognosis
  • Prostate-Specific Antigen / metabolism
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology

Substances

  • APLN protein, human
  • Apelin
  • Biomarkers, Tumor
  • Intercellular Signaling Peptides and Proteins
  • MIRN224 microRNA, human
  • MicroRNAs
  • Prostate-Specific Antigen