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Role of the lncRNA ABHD11-AS(1) in the tumorigenesis and progression of epithelial ovarian cancer through targeted regulation of RhoC

BACKGROUND: There is increasing evidence in support of the role of lncRNAs in tumor cell proliferation, differentiation and apoptosis. METHODS: We examined the expression of the lncRNA ABHD11-AS(1) in epithelial ovarian cancer (EOC) tissues and normal ovarian tissues by real-time quantitative PCR (q...

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Autores principales: Wu, Dan-Dan, Chen, Xi, Sun, Kai-Xuan, Wang, Li-Li, Chen, Shuo, Zhao, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561620/
https://www.ncbi.nlm.nih.gov/pubmed/28818073
http://dx.doi.org/10.1186/s12943-017-0709-5
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author Wu, Dan-Dan
Chen, Xi
Sun, Kai-Xuan
Wang, Li-Li
Chen, Shuo
Zhao, Yang
author_facet Wu, Dan-Dan
Chen, Xi
Sun, Kai-Xuan
Wang, Li-Li
Chen, Shuo
Zhao, Yang
author_sort Wu, Dan-Dan
collection PubMed
description BACKGROUND: There is increasing evidence in support of the role of lncRNAs in tumor cell proliferation, differentiation and apoptosis. METHODS: We examined the expression of the lncRNA ABHD11-AS(1) in epithelial ovarian cancer (EOC) tissues and normal ovarian tissues by real-time quantitative PCR (qRT-PCR). After inducing ABHD11-AS(1) downregulation by small interfering RNA (siRNA) or ABHD11-AS(1) overexpression by plasmid transfection, we examined the EOC cell phenotypes and expression of related molecules. RESULTS: Expression of the lncRNA ABHD11-AS(1) in EOC tissues was higher than that in normal ovarian tissue. It was positively associated with the tumor stage (stage I/II vs. stage III/IV), and it was lower in the well-differentiated group than in the poorly/moderately differentiated group. Overexpression of ABHD11-AS(1) in the ovarian cancer cell lines A2780 and OVCAR3 promoted ovarian cancer cell proliferation, invasion and migration, and inhibited apoptosis. Silencing of ABHD11-AS(1) had the opposite effect. Subcutaneous injection of tumor cells in nude mice showed that ABHD11-AS(1) could significantly promote tumor growth. In addition, intraperitoneal injection of tumor cells in the nude mice resulted in an increase in the metastatic ability of the tumor. Further, overexpression of ABHD11-AS(1) upregulated the expression of RhoC and its downstream molecules P70s6k, MMP2 and BCL-xL. Silencing of ABHD11-AS(1) had the opposite effect. The RNA pull-down assay showed that ABHD11-AS(1) can combine directly with RhoC. Silencing of RhoC was found to inhibit the cancer-promoting effects of lncRNA ABHD11-AS(1). Thus, it seems that RhoC is a major target of the lncRNA ABHD11-AS(1). CONCLUSIONS: This is the first study to demonstrate the role of RhoC in the tumor-promoting effects of the lncRNA ABHD11-AS(1). The present findings shed light on new therapeutic targets for ovarian cancer treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-017-0709-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-55616202017-08-18 Role of the lncRNA ABHD11-AS(1) in the tumorigenesis and progression of epithelial ovarian cancer through targeted regulation of RhoC Wu, Dan-Dan Chen, Xi Sun, Kai-Xuan Wang, Li-Li Chen, Shuo Zhao, Yang Mol Cancer Research BACKGROUND: There is increasing evidence in support of the role of lncRNAs in tumor cell proliferation, differentiation and apoptosis. METHODS: We examined the expression of the lncRNA ABHD11-AS(1) in epithelial ovarian cancer (EOC) tissues and normal ovarian tissues by real-time quantitative PCR (qRT-PCR). After inducing ABHD11-AS(1) downregulation by small interfering RNA (siRNA) or ABHD11-AS(1) overexpression by plasmid transfection, we examined the EOC cell phenotypes and expression of related molecules. RESULTS: Expression of the lncRNA ABHD11-AS(1) in EOC tissues was higher than that in normal ovarian tissue. It was positively associated with the tumor stage (stage I/II vs. stage III/IV), and it was lower in the well-differentiated group than in the poorly/moderately differentiated group. Overexpression of ABHD11-AS(1) in the ovarian cancer cell lines A2780 and OVCAR3 promoted ovarian cancer cell proliferation, invasion and migration, and inhibited apoptosis. Silencing of ABHD11-AS(1) had the opposite effect. Subcutaneous injection of tumor cells in nude mice showed that ABHD11-AS(1) could significantly promote tumor growth. In addition, intraperitoneal injection of tumor cells in the nude mice resulted in an increase in the metastatic ability of the tumor. Further, overexpression of ABHD11-AS(1) upregulated the expression of RhoC and its downstream molecules P70s6k, MMP2 and BCL-xL. Silencing of ABHD11-AS(1) had the opposite effect. The RNA pull-down assay showed that ABHD11-AS(1) can combine directly with RhoC. Silencing of RhoC was found to inhibit the cancer-promoting effects of lncRNA ABHD11-AS(1). Thus, it seems that RhoC is a major target of the lncRNA ABHD11-AS(1). CONCLUSIONS: This is the first study to demonstrate the role of RhoC in the tumor-promoting effects of the lncRNA ABHD11-AS(1). The present findings shed light on new therapeutic targets for ovarian cancer treatment. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12943-017-0709-5) contains supplementary material, which is available to authorized users. BioMed Central 2017-08-17 /pmc/articles/PMC5561620/ /pubmed/28818073 http://dx.doi.org/10.1186/s12943-017-0709-5 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Wu, Dan-Dan
Chen, Xi
Sun, Kai-Xuan
Wang, Li-Li
Chen, Shuo
Zhao, Yang
Role of the lncRNA ABHD11-AS(1) in the tumorigenesis and progression of epithelial ovarian cancer through targeted regulation of RhoC
title Role of the lncRNA ABHD11-AS(1) in the tumorigenesis and progression of epithelial ovarian cancer through targeted regulation of RhoC
title_full Role of the lncRNA ABHD11-AS(1) in the tumorigenesis and progression of epithelial ovarian cancer through targeted regulation of RhoC
title_fullStr Role of the lncRNA ABHD11-AS(1) in the tumorigenesis and progression of epithelial ovarian cancer through targeted regulation of RhoC
title_full_unstemmed Role of the lncRNA ABHD11-AS(1) in the tumorigenesis and progression of epithelial ovarian cancer through targeted regulation of RhoC
title_short Role of the lncRNA ABHD11-AS(1) in the tumorigenesis and progression of epithelial ovarian cancer through targeted regulation of RhoC
title_sort role of the lncrna abhd11-as(1) in the tumorigenesis and progression of epithelial ovarian cancer through targeted regulation of rhoc
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5561620/
https://www.ncbi.nlm.nih.gov/pubmed/28818073
http://dx.doi.org/10.1186/s12943-017-0709-5
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