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Long non-coding RNA DANCR promotes cervical cancer growth via activation of the Wnt/?-catenin signaling pathway.

ABSTRACT: Background:Long non-coding RNAs (lncRNAs) are implicated in many pathophysiological processes, including cancers. In particular, lncRNA DANCR is regarded as a cancer-associated lncRNA exerting various regulatory mechanisms. However, the expressions, functions, and mechanisms of action of DANCR in cervical cancer are still unclear. Methods:The expressions of DANCR in cervical cancer tissues and cell lines were evaluated using qRT-PCR. Correlations between DANCR expression and clinicopathological features and prognosis were analyzed. The roles of DANCR in cervical cancer growth were evaluated by in vitro CCK-8 and EdU assay, and in vivo xenograft assay. The regulatory effects of DANCR on Wnt/?-catenin signaling pathway were evaluated using nuclear proteins extraction, western blot, and qRT-PCR. Results:DANCR is increased in cervical cancer tissues and cell lines. Increased expression of DANCR is associated with large tumor size, advanced FIGO stage, and poor overall survival of cervical cancer patients. Functional experiments showed that enhanced expression of DANCR promotes cervical cancer cell proliferation in vitro and xenograft growth in vivo. Conversely, DANCR knockdown inhibits cervical cancer cell proliferation in vitro and xenograft growth in vivo. Mechanistic investigation demonstrated that DANCR upregulates the expressions of FRAT1 and FRAT2 and activates the Wnt/?-catenin signaling pathway. Blocking the Wnt/?-catenin signaling pathway abolishes the pro-proliferative roles of DANCR overexpression and anti-proliferative roles of DANCR knockdown. Conclusions:Our findings suggest DANCR as an oncogenic lncRNA in cervical cancer through activating the Wnt/?-catenin signaling pathway, and imply that DANCR may be a promising prognostic biomarker and therapeutic target for cervical cancer.

SUBMITTER: Tian W

PROVIDER: S-EPMC7036257 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Long non-coding RNA DANCR promotes cervical cancer growth via activation of the Wnt/β-catenin signaling pathway.

Tian Wanjia W Lei Ningjing N Guo Ruixia R Yuan Zhongfu Z Chang Lei L

Cancer cell international 20200222

<h4>Background</h4>Long non-coding RNAs (lncRNAs) are implicated in many pathophysiological processes, including cancers. In particular, lncRNA DANCR is regarded as a cancer-associated lncRNA exerting various regulatory mechanisms. However, the expressions, functions, and mechanisms of action of DANCR in cervical cancer are still unclear.<h4>Methods</h4>The expressions of DANCR in cervical cancer tissues and cell lines were evaluated using qRT-PCR. Correlations between DANCR expression and clini ...[more]

PMID: 32123519

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Project description:BackgroundStudies have shown that cancer susceptibility candidate 11 (CASC11), a newly discovered long non-coding RNA (lncRNA), was aberrantly overexpressed in hepatic carcinoma, gastric cancer and colorectal cancer. However, its effects on cervical cancer has been kept unknown up to now. The present study was aimed to investigate the relationship between lncRNA CASC11 and cervical cancer and further explore the mechanism of CASC11 effect on cervical cancer progression.MaterialsQuantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expressions of CASC11 in cancerous and adjacent normal tissues of patients with cervical cancer as well as in cell lines. The proliferation, migration, invasion and apoptosis were assayed after transfecting the cell with si-CASC11 or pcDNA3.1-CASC11. TOP/FOP-Flash luciferase reporter assay and western blot were used to analysis the activation of Wnt/β-catenin signaling pathway. Si-CASC11-transfected HeLa cells were subcutaneously inoculated into male athymic (nude) mice to investigate the effect of CASC11 on the tumor formation.ResultsWe discovered that CASC11, the expression of which was positively associated with the tumor size and the FIGO staging and negatively related to the patients' survival rate, was up-regulated in the cervical cancer tissues and cell lines. Silencing CASC11 inhibited the proliferation, migration as well as invasion and promoted the cell apoptosis. Conversely, overexpression of CASC11 facilitated the cancer cell's proliferation, migration and invasion ability and suppressed the apoptosis. Further study showed that CASC11 promoted the migration and invasion of cervical cancer cells by activating Wnt/β-catenin signaling pathway and silencing CASC11 inhibited the tumor growth in vivo.ConclusionOur study demonstrated that CASC11 promoted the cervical cancer progression by activating Wnt/β-catenin signaling pathway for the first time, which provides a new target or a potential diagnostic biomarker of the treatment for cervical cancer.

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Long non-coding RNA DANCR promotes cervical cancer growth via activation of the Wnt/?-catenin signaling pathway.

Publications

Long non-coding RNA DANCR promotes cervical cancer growth via activation of the Wnt/β-catenin signaling pathway.

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