Role of microRNAs in ovarian cancer pathogenesis and potential clinical implications.
Despite important improvements over the past two decades, the overall cure rate of epithelial ovarian cancer (EOC) remains only approximately 30%. Although much has been learned about the proteins and pathways involved in early events of malignant transformation and drug resistance, a major challenge still remaining is the identification of markers for early diagnosis and prediction of response to chemotherapy. Recently, it has become clear that alterations in the expression of microRNAs (miRNAs) contribute to the pathogenesis and progression of several human malignancies. In this review we discuss current data concerning the accumulating evidence of the role of miRNAs in EOC pathogenesis and tumor characterization; their dysregulated expression in EOC; and their still undefined role in diagnosis, prognosis and prediction of response to therapy. The most frequently deregulated miRNAs are members of the let-7 and miR-200 families, the latter involved in epithelial-to-mesenchymal transition (EMT). EMT is part of normal ovarian surface epithelium physiology, being the key regulator of the post-ovulatory repair process, and failure to undergo EMT may be one of the events leading to transformation. A general down-modulation of miRNA expression is observed in EOC compared to normal tissue. However, a clear consensus on the miRNA signatures associated with prognosis or prediction of response to therapy has not yet been reached.
Mezzanzanica
Delia
D
Unit of Molecular Therapies, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. delia.mezzanzanica@istitutotumori.mi.it
Bagnoli
Marina
M
De Cecco
Loris
L
Valeri
Barbara
B
Canevari
Silvana
S
D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics* / Q000473:pathology; D011379:Prognosis
D014408:Biomarkers, Tumor; D035683:MicroRNAs