OncoTargets and Therapy (Feb 2020)
GAS2 Promotes Cell Proliferation and Invasion and Suppresses Apoptosis in Pediatric T-Cell Acute Lymphoblastic Leukemia and Activates Wnt/β-Catenin Pathway
Abstract
Yan Kong, Shouyong Zhao, Hurong Tian, Yang Hai Clinical Lab, Liaocheng People’s Hospital, Liaocheng City, Shandong Province 252000, People’s Republic of ChinaCorrespondence: Hurong TianClinical Lab, Liaocheng People’s Hospital, No. 67, Dongchang West Road, Dongchangfu District, Liaocheng City, Shandong Province 252000, People’s Republic of ChinaTel +86 0635 8276172Email [email protected]: This study aimed to investigate the effect of growth arrest specific 2 (GAS2) on T-cell acute lymphoblastic leukemia (T-ALL) and its potential molecular mechanism.Methods: The GAS2 expression level was detected by qRT-RCR and Western blot in normal T lymphocytes and T-ALL cells Jurkat and CCRF-CEM. The proliferation and invasion of Jurkat and CCRF-CEM cells were detected by MTT and Transwell assay, respectively. Apoptosis and cell cycle were measured by flow cytometry. In addition, the chemotherapeutic sensitivity of Jurkat and CCRF-CEM cells was measured MTT assay and flow cytometry.Results: GAS2 was highly expressed in Jurkat and CCRF-CEM cells. GAS2 could promote cell proliferation and invasion, and inhibit apoptosis of Jurkat and CCRF-CEM cells. GAS2 also promoted cell cycle changes from G0/G1 phase to S phase in Jurkat and CCRF-CEM cells. In addition, GAS2 could reduce the chemotherapeutic sensitivity of Jurkat and CCRF-CEM cells. GAS2 overexpression could promote the expression levels of ki67, proliferating cell nuclear antigen (PCNA), Bcl-2, c-myc, cyclin D1 and β-catenin, while GAS2 knockdown could inhibit their expression levels. Meanwhile, GAS2 overexpression could inhibit Bax expression. Moreover, Wnt/β-catenin pathway inhibitor XAV939 could inhibit the expressions of c-myc, cyclin D1 and β-catenin, but activator LiCl could promote their expression.Conclusion: Our study demonstrated that GAS2 could promote cell proliferation and invasion, and induce cell cycle, as well as inhibit apoptosis and could activate the Wnt/β-catenin pathway in T-ALL cells.Keywords: T-ALL, GAS2, proliferation, apoptosis, invasion, cell cycle, Wnt/β-catenin pathway
