Long non-coding RNA MALAT1 regulates ovarian cancer cell proliferation, migration and apoptosis through Wnt/β-catenin signaling pathway

C. Guo, X. Wang, L.-P. Chen, M. Li, M. Li, Y.-H. Hu, W.-H. Ding, X. Wang

Department of Obstetrics and Gynecology, Taihe Hospital, Hubei University of Medicine, Shiyan, P.R. China. wx300@163.com

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• Oncology

OBJECTIVE: Long non-coding RNA (LncRNA) MALAT1 is an important regulatory molecule in many diseases, especially in ovarian cancer. We aimed at exploring the function of MALAT1 in ovarian cancer and at clarifying its mechanisms.

PATIENTS AND METHODS: The expression level of MALAT1 in ovarian cancer tissues, para-carcinoma tissues and ovarian cancer cell lines were analyzed by Real-time polymerase chain reaction (RT-PCR). The cell proliferation rate was detected by CCK8 assay in SKOV3 and HO8910 cells. Transwell was used to detect the invasion and migration activities in SKOV3 and HO8910 cells. The cell cycle distribution and apoptosis rate were measured by flow cytometry analysis. The expression level of Dvl2, GSK-3β, β-catenin and cyclin D1 were detected by RT-PCR and Western blot.

RESULTS: The relative expression level of MALAT1 was identified to be aberrantly up-regulated in ovarian cancer tissues and cell lines. The high expression level of MALAT1 was associated with poor prognosis in ovarian cancer patients. The down-regulation of MALAT1 inhibited cell proliferation, invasion and migration, arrested cell cycle progression in S phase and induced cell apoptosis in ovarian cancer cell lines. Meanwhile, the down-regulation of MALAT1 decreased the expression level of DVL2, β-catenin and cyclin D1 and increased the expression level of GSK-3β in SKOV3 and HO8910 cells. Moreover, the inhibitory effect of MALAT1 down-regulation in cell invasion and migration was reversed by SKL2001 activating Wnt/β-catenin signal pathway and enhanced by XAV939 inhibiting Wnt/β-catenin signal pathway.

CONCLUSIONS: MALAT1 was overexpressed in ovarian cancer and associated to the poor prognosis. The down-regulation of MALAT1 inhibited cell proliferation, invasion and migration, arrested cell cycle progression in S phase and induced cell apoptosis by restraining the activation of Wnt/β-catenin signaling pathway in ovarian cancer cells.

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