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Long non-coding RNA NPBWR1-2 affects the development of ovarian cancer via multiple microRNAs.

ABSTRACT: Ovarian cancer has a high incidence rate and mortality in gynaecologic malignancies. Epithelial ovarian cancer (EOC) accounts for >95% of ovarian cancer cases. Most of the patients with EOC are difficult to diagnose in early stage. The aim of the present study was to compare the long non-coding (lnc)RNA expression profiles of five ovarian cancer cell lines (IGROV1, A2780, SKOV3, ES2, and Hey) and an ovarian epithelial cell line (IOSE80) in order to identify differentially expressed lncRNAs and their associated microRNAs (miRNAs). The expression profiles of lncRNAs and mRNAs in these cell lines were determined by microarray gene analysis and reverse transcription-quantitative PCR. lncRNA neuropeptides B and W receptor 1-2 (NPBWR1-2) overexpression was induced in the SKOV3 cell line. Cell viability, proliferation, migration, invasion and apoptosis were evaluated using MTT, colony-formation, Transwell and flow cytometry assays, respectively. The microarray results indicated that several lncRNAs were differentially expressed in the five ovarian cancer cell lines compared with the normal ovarian epithelial cell line. Compared with IOSE80, lncRNA NPBWR1-2 was downregulated by more than two-fold in all five ovarian cancer cell lines. Moreover, NPBWR1-2 overexpression in the SKOV3 cell line decreased cell viability, inhibited proliferation, migration and invasion, and promoted apoptosis compared with the control cells. A total of 20 miRNAs, which are involved in tumorigenesis and development, were predicted to be associated with NPBWR1-2 by bioinformatics analysis. The results of the present study suggest that lncRNA NPBWR1-2 affects the occurrence and development of ovarian cancer via multiple miRNAs, providing a theoretical basis for the development of novel clinical treatments.

SUBMITTER: Liu S

PROVIDER: S-EPMC7285903 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Long non-coding RNA NPBWR1-2 affects the development of ovarian cancer via multiple microRNAs.

Liu Shasha S Du Qiuyue Q Rao Yang Y Liu Caiyan C Qu Pengpeng P

Oncology letters 20200518 1

Ovarian cancer has a high incidence rate and mortality in gynaecologic malignancies. Epithelial ovarian cancer (EOC) accounts for >95% of ovarian cancer cases. Most of the patients with EOC are difficult to diagnose in early stage. The aim of the present study was to compare the long non-coding (lnc)RNA expression profiles of five ovarian cancer cell lines (IGROV1, A2780, SKOV3, ES2, and Hey) and an ovarian epithelial cell line (IOSE80) in order to identify differentially expressed lncRNAs and t ...[more]

PMID: 32565993

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Project description:BackgroundEpithelial ovarian cancer (EOC) is a highly prevalent disease that rapidly metastasizes and has poor prognosis. Most women are in the middle or late stages when diagnosed and have low survival rates. Recently, long non-coding RNAs (lncRNAs) were recognized to play pivotal roles in the development of EOC.MethodsThe expression of SLC25A21 antisense RNA 1 (SLC25A21-AS1) and Polypyrimidine Tract Binding Protein 3 (PTBP3) in EOC cells was assessed via qPCR. The proliferation activity of these cells was detected by EdU and Cell counting kit-8 (CCK8) assays, while the death rate of apoptotic cells and the cell cycle were detected by flow cytometry. Detection of cell transfer rate by transwell assay. Protein expression was measured through western blotting. Interactions between SLC25A21-AS1 and PTBP3 were detected through RNA immunoprecipitation (RIP), IF-FISH co-localization experiments and electrophoretic mobility shift assay (EMSA). The in vivo importance of SLC25A21-AS1 as a tumor suppressor modulator was assessed using murine xenograft models.ResultsThe lncRNA SLC25A21-AS1 has negligible expression in ovarian cancer tissues compared with that in normal ovarian tissues. A series of functional experiments revealed that the upregulation of SLC25A21-AS1 markedly blocked the proliferation and metastasis of EOC cells in vitro, while its downregulation had the opposite effect. Overexpression of SLC25A21-AS1 in a nude mouse model of EOC in vivo resulted in slower tumor growth and weakened metastatic potential. Moreover, SLC25A21-AS1 reduced the protein stability of PTBP3 and promoted its degradation. A series of subsequent experiments found that SLC25A21-AS1 inhibits EOC cell proliferation and metastasis by modulating PTBP3 through the ubiquitin-proteasome pathway and that the combination of SLC25A21-AS1 and PTBP3 provides the necessary conditions for the for the function to be realized.ConclusionsOur research reveals the effect of SLC25A21-AS1 in EOC development and suggests SLC25A21-AS1 can serve as a prognostic target by promoting the degradation of PTBP3 to improve patient survival.

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Long non-coding RNA NPBWR1-2 affects the development of ovarian cancer via multiple microRNAs.

Publications

Long non-coding RNA NPBWR1-2 affects the development of ovarian cancer via multiple microRNAs.

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