MicroRNA let-7a Modifies the Effect of Self-Renewal Gene HIWI on Patient Survival of Epithelial Ovarian Cancer.

Abstract Aberrant expressions of self-renewal gene HIWI and microRNA let-7a are 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 physically binds 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.