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MiR-23a promotes IKK? expression but suppresses ST7L expression to contribute to the malignancy of epithelial ovarian cancer cells.

ABSTRACT: BACKGROUND:Dysregulation of microRNAs (miRNAs) has been found in human epithelial ovarian cancer (EOC). However, the role and mechanism of action of miR-23a in EOC remain unclear. METHODS:The roles of miR-23a, IKK?, and ST7L in EOC were determined by MTT, colony formation, wounding healing, transwell, flow cytometry, immunofluorescence, RT-qPCR, and western blotting experiments. miR-23a target genes were validated by EGFP reporter assays, RT-qPCR, and western blotting analysis. RESULTS:miR-23a is upregulated and promotes tumorigenic activity by facilitating the progress of cell cycle and EMT and repressing apoptosis in EOC cells. miR-23a enhances the expression of IKK? but suppresses the expression of ST7L by binding the 3'UTR of each transcript in EOC cells. The proliferation, migration, and invasion of EOC cells are increased by IKK? and inhibited by ST7L. Furthermore, miR-23a activates NF-?B by upregulating IKK? and WNT/MAPK pathway by downregulating ST7L. CONCLUSIONS:miR-23a functions as an oncogene by targeting IKK? and ST7L, thus contributing to the malignancy of EOC cells.

SUBMITTER: Yang Z

PROVIDER: S-EPMC5023779 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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miR-23a promotes IKKα expression but suppresses ST7L expression to contribute to the malignancy of epithelial ovarian cancer cells.

Yang Zhen Z Wang Xiang-Ling XL Bai Ru R Liu Wei-Ying WY Li Xin X Liu Min M Tang Hua H

British journal of cancer 20160818 6

<h4>Background</h4>Dysregulation of microRNAs (miRNAs) has been found in human epithelial ovarian cancer (EOC). However, the role and mechanism of action of miR-23a in EOC remain unclear.<h4>Methods</h4>The roles of miR-23a, IKKα, and ST7L in EOC were determined by MTT, colony formation, wounding healing, transwell, flow cytometry, immunofluorescence, RT-qPCR, and western blotting experiments. miR-23a target genes were validated by EGFP reporter assays, RT-qPCR, and western blotting analysis.<h4 ...[more]

PMID: 27537390

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Project description:BackgroundOvarian epithelial cancer (OEC) usually presents in the later stages of the disease. Factors, especially those associated with cell-cycle genes, affecting the genesis and tumour progression for ovarian cancer are largely unknown. We hypothesized that over-expressed transcription factors (TFs), as well as those that are driving the expression of the OEC over-expressed genes, could be the key for OEC genesis and potentially useful tissue and serum markers for malignancy associated with OEC.MethodsUsing a combination of computational (selection of candidate TF markers and malignancy prediction) and experimental approaches (tissue microarray and western blotting on patient samples) we identified and evaluated E2F5 transcription factor involved in cell proliferation, as a promising candidate regulatory target in early stage disease. Our hypothesis was supported by our tissue array experiments that showed E2F5 expression only in OEC samples but not in normal and benign tissues, and by significantly positively biased expression in serum samples done using western blotting studies.ResultsAnalysis of clinical cases shows that of the E2F5 status is characteristic for a different population group than one covered by CA125, a conventional OEC biomarker. E2F5 used in different combinations with CA125 for distinguishing malignant cyst from benign cyst shows that the presence of CA125 or E2F5 increases sensitivity of OEC detection to 97.9% (an increase from 87.5% if only CA125 is used) and, more importantly, the presence of both CA125 and E2F5 increases specificity of OEC to 72.5% (an increase from 55% if only CA125 is used). This significantly improved accuracy suggests possibility of an improved diagnostics of OEC. Furthermore, detection of malignancy status in 86 cases (38 benign, 48 early and late OEC) shows that the use of E2F5 status in combination with other clinical characteristics allows for an improved detection of malignant cases with sensitivity, specificity, F-measure and accuracy of 97.92%, 97.37%, 97.92% and 97.67%, respectively.ConclusionsOverall, our findings, in addition to opening a realistic possibility for improved OEC diagnosis, provide an indirect evidence that a cell-cycle regulatory protein E2F5 might play a significant role in OEC pathogenesis.

Dataset Information

MiR-23a promotes IKK? expression but suppresses ST7L expression to contribute to the malignancy of epithelial ovarian cancer cells.

Publications

miR-23a promotes IKKα expression but suppresses ST7L expression to contribute to the malignancy of epithelial ovarian cancer cells.

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