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- Title
Role of the lncRNA ABHD11-AS in the tumorigenesis and progression of epithelial ovarian cancer through targeted regulation of RhoC.
- Authors
Dan-Dan Wu; Xi Chen; Kai-Xuan Sun; Li-Li Wang; Shuo Chen; Yang Zhao
- Abstract
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 in epithelial ovarian cancer (EOC) tissues and normal ovarian tissues by real-time quantitative PCR (qRT-PCR). After inducing ABHD11-AS downregulation by small interfering RNA (siRNA) or ABHD11-AS overexpression by plasmid transfection, we examined the EOC cell phenotypes and expression of related molecules. Results: Expression of the lncRNA ABHD11-AS 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 in the ovarian cancer cell lines A2780 and OVCAR3 promoted ovarian cancer cell proliferation, invasion and migration, and inhibited apoptosis. Silencing of ABHD11-AS had the opposite effect. Subcutaneous injection of tumor cells in nude mice showed that ABHD11-AS 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 upregulated the expression of RhoC and its downstream molecules P70s6k, MMP2 and BCL-xL. Silencing of ABHD11-AS had the opposite effect. The RNA pull-down assay showed that ABHD11-AS can combine directly with RhoC. Silencing of RhoC was found to inhibit the cancer-promoting effects of lncRNA ABHD11-AS. Thus, it seems that RhoC is a major target of the lncRNA ABHD11-AS. Conclusions: This is the first study to demonstrate the role of RhoC in the tumor-promoting effects of the lncRNA ABHD11-AS. The present findings shed light on new therapeutic targets for ovarian cancer treatment.
- Subjects
OVARIAN epithelial cancer; SMALL interfering RNA; NEOPLASTIC cell transformation; HYDROLASES regulation; CELL proliferation; GENETIC overexpression; RHO GTPases
- Publication
Molecular Cancer, 2017, Vol 16, Issue 1, p1
- ISSN
1476-4598
- Publication type
Article
- DOI
10.1186/s12943-017-0709-5