MicroRNA let-7a modifies the effect of self-renewal gene HIWI on patient survival of epithelial ovarian cancer

Mol Carcinog. 2016 Apr;55(4):357-65. doi: 10.1002/mc.22285. Epub 2015 Jan 28.

Abstract

Aberrant expressions of self-renewal gene HIWI and microRNA (miRNA) let-7a are observed in epithelial ovarian cancer (EOC). A U-shape association between HIWI expression and overall survival is seen in several human cancers but unknown in EOC. HIWI directly and/or indirectly interacts with let-7a, but the clinical relevance of this interaction is yet to be addressed. Here, we analyzed HIWI and let-7a expressions in 211 primary EOC tissues using quantitative reverse-transcription PCR to investigate HIWI and its interaction with let-7a in the prognostic significance of EOC. Associations of HIWI and its interaction with miRNA let-7a with patient survival were analyzed using the Kaplan-Meier survival curves and Cox proportional hazard regression models. Kaplan-Meier survival curves showed that patients with medium HIWI had poorer overall survival than those with low or high HIWI. An 89% increased death risk (HR = 1.89, 95% CI: 1.29-2.98) was observed in the medium HIWI group in multivariate Cox proportional hazard regression analyses. Among patients with high let-7a expression, those with medium HIWI had an increased risk of death compared to those with low HIWI (HR = 2.62, 95% CI: 1.30-5.30), whereas among those with low let-7a, no significant association between HIWI expression and overall survival was observed (HR = 1.63, 95% CI: 0.86-3.08). Moreover, HIWI expression also affected chemotherapy response. The results suggested that miRNA let-7a could modify the effect of HIWI expression on patient survival of EOC, expanding our understanding of the clinical relevance of HIWI and let-7a interaction in EOC prognosis. © 2015 Wiley Periodicals, Inc.

Keywords: epithelial ovarian cancer; let-7a; piwi-like RNA-mediated gene silencing 1 (PIWIL1 or HIWI); prognosis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Argonaute Proteins / genetics*
  • Carcinoma, Ovarian Epithelial
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / diagnosis*
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Ovary / metabolism
  • Ovary / pathology*
  • Prognosis

Substances

  • Argonaute Proteins
  • MicroRNAs
  • PIWIL1 protein, human
  • mirnlet7 microRNA, human