Abstract
BackgroundSerous epithelial ovarian cancer (SEOC) is a highly metastatic disease and its progression has been implicated with microRNAs. This study aimed to identify the differentially expressed microRNAs in Malaysian patients with SEOC and examine the microRNAs functional roles in SEOC cells.MethodsTwenty-two SEOC and twenty-two normal samples were subjected to miRNA expression profiling using the locked nucleic acid (LNA) quantitative real-time PCR (qPCR). The localization of miR-200c was determined via LNA in situ hybridization (ISH). Functional analysis of miR-200c and miR-31 on cell proliferation, migration and invasion and clonogenic cell survival were assessed in vitro. The putative target genes of the two miRNAs were predicted by miRWalk program and expression of the target genes in SEOC cell lines was validated.ResultsThe miRNA expression profiling revealed thirty-eight significantly dysregulated miRNAs in SEOC compared to normal ovarian tissues. Of these, eighteen were up-regulated whilst twenty miRNAs were down-regulated. We observed chromogenic miR-200c-ISH signal predominantly in the cytoplasmic compartment of both epithelial and inflammatory cancer cells. Re-expression of miR-200c significantly increased the cell proliferation and colony formation but reduced the migration and invasion of SEOC cells. In addition, miR-200c expression was inversely proportionate with the expression of deleted in liver cancer-1 (DLC-1) gene. Over-expression of miR-31 in SEOC cells resulted in decreased cell proliferation, clonogenic potential, cell migration and invasion. Meanwhile, miR-31 gain-of-function led to the down-regulation of AF4/FMR2 family member 1 (AFF1) gene.ConclusionsThese data suggested that miR-200c and miR-31 may play roles in the SEOC metastasis biology and could be considered as promising targets for therapeutic purposes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13048-015-0186-7) contains supplementary material, which is available to authorized users.
Highlights
Serous epithelial ovarian cancer (SEOC) is a highly metastatic disease and its progression has been implicated with microRNAs
Since miR-31 known for its complex expression and described as a master regulator of metastasis [19], we aimed to study the roles of miR-31 in regulating SEOC
Expressed miRNAs in metastatic SEOC versus normal ovary LNATM-quantitative real-time PCR (qPCR) was performed in order to determine the dysregulated miRNAs in SEOC and normal ovarian tissues
Summary
Serous epithelial ovarian cancer (SEOC) is a highly metastatic disease and its progression has been implicated with microRNAs. Ovarian cancer ranks as the third most common gynaecological malignancy worldwide with approximately 225,000 new cases been reported in 2011 [1]. This malignancy represents the fourth most frequently diagnosed in Malaysia and becoming a major cause of deaths in Malaysian women [2]. Ibrahim et al Journal of Ovarian Research (2015) 8:56 untranslated region of the target mRNA [7]. As master regulators of gene expression, miRNAs can act as oncomiRs or tumor suppressor miRNAs depending on their gene targets, and alterations of miRNAs expression promote cancer development and progression [10]
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