Circular RNA TTBK2 regulates cell proliferation, invasion and ferroptosis via miR-761/ITGB8 axis in glioma

H.-Y. Zhang, B.-W. Zhang, Z.-B. Zhang, Q.-J. Deng

Department of Precision Medicine Center, Tianjin Medical University General Hospital, Tianjin, China. worbwt@163.com

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• Oncology

OBJECTIVE: Glioma is a primary intracranial tumor with an unfavorable prognosis. Evolving evidence indicates that circular RNA Tau tubulin kinase 2 (circ-TTBK2) is a cancer-associated gene. Therefore, this study was to explore the potential role of circ-TTBK2.

MATERIALS AND METHODS: Levels of circ-TTBK2, microRNA (miR)-761, and integrin subunit beta 8 (ITGB8) were determined by adopting quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to detect cell viability, and the invaded cells were distinguished utilizing transwell assay. Iron and lipid reactive oxygen species (ROS) assays were implemented to examine the iron (total iron and ferrous iron) and lipid-based ROS in glioma cells, respectively. Besides, dual-luciferase reporter assay was administrated to illustrate the interaction between miR-761 and circ-TTBK2 or ITGB8. The role of circ-TTBK2 was identified via xenograft tumor model.

RESULTS: Levels of circ-TTBK2 and ITGB8 were upregulated, whereas miR-761 level was low-expressed in glioma tissues and cells. Circ-TTBK2 was a sponge of miR-761 to modulate ITGB8. Additionally, circ-TTBK2 knockdown or miR-761 increase could retard cell proliferation, invasion, and promote ferroptosis in glioma cells. Interestingly, miR-761 inhibitor could abolish the repressive impact of circ-TTBK2 silencing on cell growth in vitro. Also, the influence of miR-761 mimic on cell phenotypes was regained after ITGB8 upregulation. Meanwhile, circ-TTBK2 deficiency caused the decrease of tumor growth.

CONCLUSIONS: Circ-TTBK2 regulated cell proliferation, invasion and ferroptosis via targeting ITGB8 by sponging miR-761 in glioma, providing a promising biomarker for the clinical therapy of human glioma.

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