miR-200a Overexpression in Advanced Ovarian Carcinomas as a Prognostic Indicator

Background: miR-200a expression is frequently altered in numerous cancers. The aim of the present studywas to determine the role of microRNA-200a in advanced ovarian carcinomas. Materials and
Methods: Wemeasured miR-200a expression in 72 matched normal ovarian tissues and advanced ovarian carcinomas, andalso two ovarian carcinoma cell lines (SKOV3 and SKOV3.ip1 - the latter being more invasive and metastaticthan the parental SKOV3) by stem-loop real-time RT-PCR based on TaqMan microRNA assay using U6 as areference. Levels of miR-200a expression were compared by disease stage, tumor grade, histology, and lymphnode involvement. To evaluate the role of microRNA-200a, cell proliferation and invasion of SKOV-3 andSKOV-3.ip1 were analyzed with miR-200a inhibitor/mimic transfected cells.
Results: Of 72 paired samples,65 cancer tissues overexpressed microRNA-200a greater than two fold in comparison with matched normalepithelium. Specifically, patients with lymph node metastasis showed significant elevation. The level correlatedwith clinicopathological features, including high tumor grade, late disease stage, most notably with lymph nodemetastasis, but not with tumor histology. In addition, SKOV-3.ip1 cells also overexpressed miR-200a comparedwith SKOV-3, and miR-200a inhibitor transfected SKOV-3.ip1 cells showed significant reduction in cellularproliferation and invasion, while a miR-200a mimic stimulated the opposite behavior.
Conclusions: We providedefinitive evidence that miR-200a is up-regulated in a significant proportion of advanced ovarian carcinomas,and that elevated miR-200a expression facilitates tumor progression. Our findings support the notion that miR-200a is an onco-microRNA for ovarian cancer, and elevation is a useful potential diagnostic indicator. This studyalso provides a solid basis for further functional analysis of miR-200a in advanced ovarian cancer.