Long noncoding RNA PCAT6 regulates cell growth and metastasis via Wnt/β-catenin pathway and is a prognosis marker in cervical cancer

X.-J. Lv, Q. Tang, Y.-Q. Tu, D.-D. Yan, Q.-C. Wei

Department of Radiation Oncology, the Second Affiliated Hospital, Zhejiang University School of  Medicine, Zhejiang University, Hangzhou, Zhejiang, China. Qichun_Wei@zju.edu.cn

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• Oncology

OBJECTIVE: Previously, long noncoding RNAs (lncRNAs) have been reported to have critical regulatory roles in the progression of human cancers. LncRNA prostate cancer-associated transcript 6 (PCAT6) has been reported to act as an oncogene in several tumors. However, its expression and function in cervical cancer (CC) have not been investigated. In this study, we aim to reveal the functions of PCAT6 and the underlying mechanisms in CC.

PATIENTS AND METHODS: We evaluated the expression levels of PCAT6 in CC tissues and cell lines using real-time PCR. The clinical data were interpreted by chi-square test, Kaplan-Meier survival analyses, univariate analysis, and multivariate analysis. The effect of PCAT6 on CC proliferation and metastasis was investigated by CCK-8 assay, EdU incorporation assay and transwell assay. The cell apoptosis was detected by apoptosis flow detection. RT-PCR and Western blotting were used to detect the expression levels of β-catenin, cyclin D1 and c-myc.

RESULTS: We found that PCAT6 expression was significantly up-regulated in human CC tissues and cell lines compared with their normal counterparts, and its high levels were associated with advanced FIGO stage, depth of cervical invasion and positively lymph node metastasis. Survival assays indicated that high PCAT6 expression had a negative influence on overall survival and disease-free survival. Moreover, multivariate analysis identified high PCAT6 expression as an unfavorable prognostic biomarker for CC patients. Functionally, knockdown of PCAT6 significantly suppressed CC cells proliferation, migration and invasion, and promoted apoptosis. Mechanistic investigation showed PCAT6 activates Wnt/β-catenin signaling in CC cell lines by promoting the expression of β-catenin, cyclin D1 and c-myc.

CONCLUSIONS: Our results indicated that PCAT6 played oncogenic roles and can be used as a therapeutic target for treating human CC.

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