MicroRNA in Ovarian Cancer: Biology, Pathogenesis, and Therapeutic Opportunities

Abstract

Ovarian cancer comprises one of the three major malignant tumor types in the female reproductive system. The mortality rate of this cancer is the highest among all gynecological tumors, with ovarian cancer metastasis constituting an important cause of death. Therefore, markers for disease prediction and prognosis are highly desirable for early diagnosis as well as for helping optimize and personalize treatment. Recently, microRNAs (miRNAs), which consist of short-sequence RNAs that do not encode a protein, have emerged as new biomarkers in the clinical diagnosis and treatment of ovarian cancer. By pairing with bases specific to the target messenger RNA (mRNA), miRNAs cause degradation of the target mRNA or inhibit its translation, thereby regulating various cellular processes including cell proliferation and adhesion. Increasing numbers of studies have shown that miRNA expression abnormality plays an important role in the development of ovarian cancer. In this review, we discuss the mechanisms of miRNA action, current research regarding their role in the suppression or promotion of ovarian cancer, and their use as markers for diagnosis of prognosis or as therapeutic targets for this disease. Finally, we present future perspectives regarding the clinical management of ovarian cancer and the role for miRNAs therein.

Keywords: diagnosis; microRNA; ovarian cancer; prognosis.

Figure 1

An overview of miRNA biogenesis and effector pathways. The transcription of a primary miRNA (pri-miRNA) by RNA polymerase II is followed by its processing by Drosha in complex into a precursor hairpin (pre-miRNA); these steps occur in the nucleus. Following transportation by Exportin from nucleus to cytoplasm, the pre-miRNAs are processed by Dicer. A miRNA-loaded RNA-induced silencing complex (RISC) mediates gene silencing via mRNA cleavage and degradation or translational repression, depending on the complementarity between the miRNA and the targeted mRNA transcript. The result is either the inhibition of translation or the degradation of the mRNA target, depending on incomplete or complete complementarity to the target mRNA sequence.