Differential MicroRNA Expression Profiles in Primary and Recurrent Epithelial Ovarian Cancer.

Although it has been shown that microRNAs influence messenger RNA post-transcriptional control and can attribute to human tumorigenesis, little is known regarading the differences in microRNA expression between primary and recurrent epithelial ovarian cancer (EOC). The purpose of the present study was to assess the differential expression of microRNA between primary and recurrent EOC. Between September 2013 and May 2014, the expression of microRNAs in tumor tissues from 5 primary and 5 recurrent EOC cases were analyzed. The tumor histotype was serous cystadenocarcinoma in all patients. Total RNA was extracted from tumor samples and microRNA expression levels were measured by performing microarray analysis. Expression levels were compared between the two groups and analyzed statistically. Several microRNAs were differentially expressed in recurrent EOC compared to primary EOC, including 18 under-expressed microRNAs and 33 over-expressed microRNAs among 6,658 human microRNAs. Four specific microRNAs were the most significantly over-expressed in recurrent EOC: miR-551b, miR-19b, miR-196b and miR-3198. Moreover, 4 specific microRNAs were the most significantly down-expressed in recurrent EOC: miR-8084, miR-3201, miR-3613 and miR-7515. Based on our data, dysregulation of microRNA expression was associated with the recurrence of EOC. Moreover, significantly over- and down-regulated microRNAs can be useful biomarkers for the prediction of recurrence in EOC.

Chong GO ，Jeon HS ，Han HS ，Son JW ，Lee YH ，Hong DG ，Lee YS ，Cho YL ... -  《-》

Overexpression of microRNA-196b Accelerates Invasiveness of Cancer Cells in Recurrent Epithelial Ovarian Cancer Through Regulation of Homeobox A9.

Although microRNAs (miRNAs) are known to influence messenger RNA post-transcriptional control and contribute to human tumorigenesis, little is known about the differences in miRNA expression between primary and recurrent epithelial ovarian cancer (EOC). The purpose of this study was to assess the differential miRNA expression between primary and recurrent EOC and to investigate whether miR-196b could regulate the expression of the Homeobox A9 (HOXA9) gene, and thus affect the invasiveness of cancer cells in recurrent EOC. Microarrays were used to generate the expression profiles of 6658 miRNAs from samples of 10 patients with EOC. miRNA expression patterns were compared between primary and recurrent EOC. Aberrantly expressed miRNA, associated genes, and invasion activities were validated by a luciferase assay and an in vitro invasion assay. miRNA microarray analysis identified 33 overexpressed miRNAs (including miR-196b) and 18 under expressed miRNAs in recurrent EOC from 6658 human miRNAs. HOXA9 expression was inversely correlated with miR-196b levels in recurrent EOC. We noted that miR-196b induced ovarian cancer cell invasiveness in recurrent EOC by an in vitro invasion assay. Overexpression of miR-196b may contribute to invasion activities in recurrent EOC by regulating the HOXA9 gene. Moreover, miR-196b can be a potential biomarker in recurrent EOC.

Chong GO ，Jeon HS ，Han HS ，Son JW ，Lee YH ，Hong DG ，Park HJ ，Lee YS ，Cho YL ... -  《-》

MiR-135a functions as a tumor suppressor in epithelial ovarian cancer and regulates HOXA10 expression.

The activation of homeobox A10 (HOXA10) has been proved to be an important event in epithelial ovarian carcinogenesis, yet its regulation in epithelial ovarian cancer (EOC) is still not fully understood. Here, we aimed to reveal the mechanism that a predicted target miRNA regulates HOXA10 expression and the association of its expression with progression of EOC. Here, by using computer-assisted algorithms from PicTar, TargetScan, and miRBase, we identified that the predicted target miRNA of HOXA10 was miR-135a. MiR-135a expression in EOC tissues and controls was measured with quantitative RT-PCR. The role of miR-135a and HOXA10 in the growth and survival of several EOC cell lines was determined with several in vitro approaches. We found that miR-135a expression was downregulated in an EOC patient cohort. Also, patients with low miR-135a expression had shorter overall survival and progression-free survival durations than those with high expression. Functional analysis of three EOC-derived cell lines (SKOV-3, HEY, and OVCAR-3) demonstrated that miR-135a directly regulated HOXA10 expression by targeting its 3'-UTR. Inhibition of HOXA10 expression with miR-135a mimics and HOXA10 siRNA consistently resulted in cell apoptosis with concomitant enhancement of caspase-3, increase of p53 expression and reduction of Bcl-2 expression, and also suppressed cell growth and adhesion. These findings suggest that ubiquitous loss of miR-135a expression is a critical mechanism for the overexpression of HOXA10 in EOC cells, which is implicated in epithelial ovarian carcinogenesis. Furthermore, miR-135a may be predictive of EOC prognosis.

Tang W ，Jiang Y ，Mu X ，Xu L ，Cheng W ，Wang X ... -  《-》

MicroRNA-150 predicts a favorable prognosis in patients with epithelial ovarian cancer, and inhibits cell invasion and metastasis by suppressing transcriptional repressor ZEB1.

Jin M ，Yang Z ，Ye W ，Xu H ，Hua X ... -  《PLoS One》

Potential biomarker of circulating hsa-miR-1273g-3p level for detection of recurrent epithelial ovarian cancer.

Günel T ，Gumusoglu E ，Dogan B ，Ertem FB ，Hosseini MK ，Cevik N ，Senol T ，Topuz S ，Aydinli K ... -  《-》