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

• Published in: Molecular carcinogenesis 2016-04, Vol.55 (4), p.357-365
• Main Authors: Lu, Lingeng, Katsaros, Dionyssios, Risch, Harvey A., Canuto, Emilie Marion, Biglia, Nicoletta, Yu, Herbert
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Argonaute Proteins - genetics; Carcinoma, Ovarian Epithelial; epithelial ovarian cancer; Female; Gene expression; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; let-7a; Medical prognosis; MicroRNAs; MicroRNAs - genetics; Middle Aged; Neoplasms, Glandular and Epithelial - diagnosis; Neoplasms, Glandular and Epithelial - genetics; Neoplasms, Glandular and Epithelial - pathology; Ovarian cancer; Ovarian Neoplasms - diagnosis; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Ovary - metabolism; Ovary - pathology; piwi-like RNA-mediated gene silencing 1 (PIWIL1 or HIWI); Prognosis
• ISSN: 0899-1987; 1098-2744
• DOI: 10.1002/mc.22285

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.