MicroRNAs and Recent Insights into Pediatric Ovarian Cancers

Abstract

Ovarian cancer is the most common pediatric gynecologic malignancy. When diagnosed in children, ovarian cancers present unique challenges that differ dramatically from those faced by adults. Here, we review the spectrum of ovarian cancers found in young women and girls and discuss the biology of these diseases. A number of advances have recently shed significant new understanding on the potential causes of ovarian cancer in this unique population. Particular emphasis is placed on understanding how altered expression of non-coding RNA transcripts known as microRNAs play a key role in the etiology of ovarian germ cell and sex cord-stromal tumors. Emerging transgenic models for these diseases are also reviewed. Lastly, future challenges and opportunities for understanding pediatric ovarian cancers, delineating clinically useful biomarkers, and developing targeted therapies are discussed.

Keywords: DICER1; FOXL2; germ cell tumors; granulosa cell tumors; microRNA; ovarian cancer; sex cord-stromal tumors.

Figure 1

MicroRNA Biogenesis and Function. Most human miRNAs are initially transcribed as long precursors known as pri-miRNAs. Pri-miRNAs undergo a series of processing events that ultimately result in the cytoplasmic release of a mature double-stranded miRNA. Key events in miRNA biogenesis include active export of pre-miRNAs from the nucleus via a nuclear membrane complex that includes RANGAP1 and RANBP1. Once within the cytoplasm, pre-miRNAs undergo endonucleolytic cleavage by DICER1. Recent evidence now suggests that passenger miRNA strands may actively target patterns of gene expression rather than undergoing degradation. hAGO2, human Argonaut; RISC, RNA-induced Silencing Complex.