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

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

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Department of Chronic Disease Epidemiology, Yale School of Public Health, School of Medicine, Yale Cancer Center, Yale University, New Haven, Connecticut.
Department of Surgical Science, A O Città della Salute e della Scienza di Torino, S. Anna Hospital, Turin, Italy.
Department of Surgical Science, Division of Obstetrics and Gynecology, University of Torino School of Medicine, Mauriziano Hospital, Turin, Italy.
Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.


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.


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

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