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CCAT-1 promotes proliferation and inhibits apoptosis of cervical cancer cells via the Wnt signaling pathway.

ABSTRACT: Though the long noncoding RNA colon cancer associated transcript-1 (CCAT-1) has been shown to be involved in tumors of other tissues, its involvement in cervical cancer is still unknown. Therefore, the aim of this study was to investigate the molecular mechanism of CCAT-1 in cervical cancer. We quantified the expression of CCAT-1 long noncoding RNA in samples of cervical cancer tissue by real-time PCR. Effects of CCAT-1 expression on the proliferation and apoptosis of HeLa and CaSki cells were assessed by cell-count, colony-formation, and flow cytometry assays. Binding of the c-Myc protein to the CCAT-1 promoter was confirmed by chromatin immunoprecipitation. Finally, TOP-Flash and western blotting were used to examine the regulation of the Wnt/?-catenin pathway by CCAT-1. The results showed that compared with adjacent normal tissue, the expression of CCAT-1 in cervical cancer tissue was significantly upregulated. CCAT-1 expression was related to the stage and size of the tumor and recurrence prognosis. Then, we showed through functional assays that CCAT-1 could promote proliferation and inhibit apoptosis of cervical cancer cells. Furthermore, chromatin immunoprecipitation showed that c-Myc protein could promote CCAT-1 expression by binding to its promoter. Finally, fluorescent-reporter assays and western blotting showed that CCAT-1 could activate the Wnt/?-catenin pathway. In conclusion, we showed that CCAT-1 can be activated by the c-Myc protein and it can promote proliferation and inhibit apoptosis in cervical cancer cells by regulating the Wnt/?-catenin pathway. CCAT-1 might serve as a good prognostic indicator and target for treatment of cervical cancer.

SUBMITTER: Zhang J

PROVIDER: S-EPMC5620236 | biostudies-other | 2017 Sep

REPOSITORIES: biostudies-other

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CCAT-1 promotes proliferation and inhibits apoptosis of cervical cancer cells via the Wnt signaling pathway.

Zhang Jun J Gao Yali Y

Oncotarget 20170710 40

Though the long noncoding RNA colon cancer associated transcript-1 (CCAT-1) has been shown to be involved in tumors of other tissues, its involvement in cervical cancer is still unknown. Therefore, the aim of this study was to investigate the molecular mechanism of CCAT-1 in cervical cancer. We quantified the expression of CCAT-1 long noncoding RNA in samples of cervical cancer tissue by real-time PCR. Effects of CCAT-1 expression on the proliferation and apoptosis of HeLa a ...[more]

PMID: 28978096

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Project description:Background The deubiquitinating (DUB) enzyme ubiquitin-specific protease 18 (USP18), also known as UBP43, is an ubiquitin-specific protease linked to several human malignancies. However, USP18’s underlying function in human cervical cancer remains unclear. In the current study, we aimed to analyse the role of USP18 and its signalling pathways in cervical cancer. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining were performed to analyse USP18 levels in cervical cancer and matched to adjacent normal tissues. Moreover, RNA interference (RNAi) and lentiviral-mediated vector transfections were performed to silence and overexpress USP18, respectively, in cervical cancer cells. Further, Cell Counting Kit-8 (CCK-8) and Annexin V/PI staining assays were used to assess its biological function in cell proliferation and apoptosis, respectively. A xenograft model was used to examine USP18’s function in vivo. Results The present findings demonstrated that USP18 was overexpressed in cervical cancer specimens and cell lines. Silencing USP18 in SiHa and Caski cervical cancer cell lines inhibited cell proliferation, induced apoptosis, and promoted cleaved caspase-3 expression. In contrast, USP18 overexpression showed the opposite effects in human HcerEpic cells. A Gene Set Enrichment Analysis revealed that USP18 was enriched in the PI3K/AKT signalling pathway in cervical cancer. Hence, the PI3K/AKT inhibitor LY294002 was used to determine the relationship between USP18 and AKT in cervical cancer cells. Importantly, LY294002 significantly abolished the effects of USP18 overexpression in cervical cancer cells. In vivo, USP18 silencing inhibited human cervical cancer cells’ tumorigenicity. Conclusions The current study indicates that USP18 is an oncogenic gene in cervical cancer. Our findings not only deepened the understanding of USP18’s biological function in cervical cancer pathogenesis, but we also provided novel insight for cervical cancer therapy. Trial registration Retrospectively registered.

Project description:BackgroundBufadienolides derived from the skin of toads are often regarded as the main active components with antitumor effects. 19-Hydroxybufalin (19-HB) is a monomer of bufadienolides; however, its effects and underlying molecular mechanisms on tumor growth remain to be ascertained. In this report, we focused on the antitumor effects of 19-HB on non-small cell lung cancer to provide a scientific basis for its further development and utilization.MethodsThe antitumor effects of 19-HB on the human NSCLC cell lines NCI-H1299 and NCI-H838 were examined in vitro. The cells were treated with different concentrations of 19-HB, and the inhibition of cell growth was measured by CCK-8 and colony formation assays. Furthermore, cell apoptosis was analyzed by flow cytometry, TUNEL staining, JC-1 staining, and western blotting. The effects on migration and invasion were evaluated by wound-healing assay, transwell assay, and western blotting. Finally, the antitumor effects of 19-HB were evaluated in vivo using a xenograft mouse model.Results19-HB-treated NSCLC cells showed inhibited cell viability and increased apoptosis. The expression levels of cleaved caspase-3, cleaved-PARP, and Bax/Bcl-2 were upregulated, while the mitochondrial membrane potential decreased. In contrast, migration, invasion, as well as the expression of MMP2, MMP7, MMP9, the epithelial-mesenchymal transition-related proteins N-cadherin and Vimentin, and the transcription factors Snail and Slug were inhibited. Furthermore, the expression levels of the key molecules in the Wnt/β-catenin signaling pathway (CyclinD1, c-Myc, and β-catenin) were decreased. In vivo, the growth of xenograft tumors in nude mice was also significantly inhibited by 19-HB, and there were no significant changes in biochemical indicators of hepatic and renal function.Conclusions19-HB inhibited the proliferation, migration, and invasion, and promoted the apoptosis of NSCLC cells via the Wnt/β-catenin pathway. In addition, 19-HB inhibited the growth of xenograft tumors in nude mice with little toxicity to the liver and kidney. Thus, 19-HB may be a potential antitumor agent for treating NSCLC.

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CCAT-1 promotes proliferation and inhibits apoptosis of cervical cancer cells via the Wnt signaling pathway.

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<i>CCAT-1</i> promotes proliferation and inhibits apoptosis of cervical cancer cells via the Wnt signaling pathway.

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