Circ-0001801 contributes to cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT) in glioblastoma by regulating miR-628-5p/HMGB3 axis

W.-L. Chen, L. Jiang, J.-S. Wang, C.-X. Liao

Department of Neurosurgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. youxiahuinian00@126.com

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• Oncology

OBJECTIVE: Glioblastoma (GBM) is a fast-growing type of central nervous system tumor with high invasiveness and recurrence. Circular RNA (circRNA) circ-0001801 (also named as circPCMTD1) was recognized as a novel biomarker in cancers. However, the pathological mechanism of circ-0001801 in GBM is still largely obscured. To the best of our knowledge, it is the first time to reveal the involvement of circ-0001801/miR-628-5p/HMGB3 axis in the progression of GBM cells.

PATIENTS AND METHODS: Expression of circ-0001801, microRNA (miR)-628-5p and high mobility group box 3 (HMGB3) in GBM tumors and cells was detected by quantitative real time-polymerase chain reaction (qRT-PCR). Stability of circ-0001801 was determined by RNase R. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) was performed to analyze cell viability. Cell migration and invasion were assessed using transwell assay. The interaction between miR-628-5p and circ-0001801 or HMGB3 was confirmed by Dual-Luciferase reporter system. Protein expression of HMGB3, N-cadherin, E-cadherin and Vimentin was detected by Western blot.

RESULTS: The up-regulation of circ-0001801 and HMGB3 and the down-regulation of miR-628-5p were both observed in GBM tumors and cells compared with the normal ones. Depletion of circ-0001801 reduced GBM cell proliferation, migration, invasion and EMT. In addition, we discovered that circ-0001801 was a sponge of miR-628-5p and HMGB3 was a target of miR-628-5p. Furthermore, miR-628-5p inhibitor abolished circ-0001801 silencing-mediated inhibition of cell progression in GBM. Similarly, HMGB3 restored circ-0001801 silencing-mediated repression on GBM cell progression. We also noticed that circ-0001801 could improve HMGB3 expression by sponging miR-628-5p in GBM.

CONCLUSIONS: Overexpression of circ-00018 01 accelerates cell proliferation, migration, invasion and EMT in GBM by absorbing miR-628-5p and facilitating HMGB3 expression, representing promising targeted therapy for GBM.

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