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

摘要

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. 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/β-catenin signaling pathway were evaluated using nuclear proteins extraction, western blot, and qRT-PCR. 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/β-catenin signaling pathway. Blocking the Wnt/β-catenin signaling pathway abolishes the pro-proliferative roles of DANCR overexpression and anti-proliferative roles of DANCR knockdown. Our findings suggest DANCR as an oncogenic lncRNA in cervical cancer through activating the Wnt/β-catenin signaling pathway, and imply that DANCR may be a promising prognostic biomarker and therapeutic target for cervical cancer.