Long non-coding RNA H19 regulates the development of gliomas through the Wnt/β-catenin signaling pathway

N. Guan, R. Wang, W.-S. Guo, Y.-J. Lai, Y.-D. Zhang, Y.-Y. Cheng

Neurosurgery, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China. chengyy@cqmu.edu.cn

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• Oncology

OBJECTIVE: We investigated the effects of long non-coding RNA (lncRNA) H19 on glioma cell proliferation, invasion, migration, and apoptosis and the underlying mechanisms.
PATIENTS AND METHODS: H19 expression in glioma tissues, para-carcinoma tissues, and glioma cell lines was analyzed by Real-time polymerase chain reaction (RT-PCR). After transfecting U251 and U87MG cells with siRNA-H19, cell proliferation was detected by the cell counting kit-8 (CCK8) assay. Invasion and migration were detected by a transwell assay; cell cycle distribution and apoptosis were measured by flow cytometry analysis; Dvl2, GSK-3β, cyclin D1, and β-catenin expressions were detected by RT-PCR and Western blotting.
RESULTS: H19 expression in glioma tissues was higher than that in para-carcinoma tissues and associated with poor prognosis in glioma patients. Cell proliferation, invasion, and migration significantly decreased, the percentage of glioma cells in G0/G1 significantly increased, the percentage of glioma cells in the S phase significantly decreased, and apoptosis significantly increased in U251 and U87MG cells transfected with siRNA-H19 compared to those in the siRNA-NC group. Downregulation of H19 decreased DVL2, cyclin D1, and β-catenin expression and increased GSK-3β expression. The inhibitory effects of downregulation of H19 on glioma cell proliferation, invasion, and migration were reversed by SKL2001 via the activation of the Wnt/β-catenin signal pathway, which was further enhanced by inhibition of the Wnt/β-catenin signal pathway by XAV939.
CONCLUSIONS: H19 was overexpressed in glioma tissues and glioma cell lines. Downregulation of H19 inhibited cell proliferation, invasion, and migration, arrested cell cycle progression in the G0/G1 phase, and induced cell apoptosis by restraining activation of the Wnt/β-catenin signaling pathway in glioma cells. Therefore, H19 is a potential therapeutic target for glioma therapy.

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