OncoTargets and Therapy (Oct 2020)
NR5A2 Promotes Cell Growth and Resistance to Temozolomide Through Regulating Notch Signal Pathway in Glioma
Abstract
Quanxi Yang,1 Lei Deng,2 Jialiang Li,1 Pengfei Miao,1 Wenxiang Liu,1 Qi Huang1 1Department of Neurosurgery, The First People’s Hospital of Shangqiu in Henan Province, Shangqiu Clinical College, Xuzhou Medical University, Shangqiu 476100, People’s Republic of China; 2Department of Neonatology, The First People’s Hospital of Shangqiu in Henan Province, Shangqiu Clinical College, Xuzhou Medical University, Shangqiu 476100, People’s Republic of ChinaCorrespondence: Quanxi YangDepartment of Neurosurgery, The First People’s Hospital of Shangqiu in Henan Province, Shangqiu Clinical College, Xuzhou Medical University, No. 292 South Kaixuan Road, Shangqiu 476100, People’s Republic of ChinaTel +86-17737590198Email [email protected]: Glioma is a fatal primary malignant tumor. We aimed to explore the effect of nuclear receptor subfamily 5 group A member 2 (NR5A2) on glioma.Methods: NR5A2 expression in glioma tissues and cells was detected using qRT-PCR and immunohistochemistry (IHC)/Western blot. SPSS 22.0 was performed to explore the relationship between NR5A2 expression and glioma clinicopathologic features. The down-expressed plasmid of NR5A2 was transfected into glioma cells, and the cell viability, proliferation, apoptosis, migration, and invasion were respectively determined by MTT, EdU, flow cytometry, wound healing and transwell assays. Cell cycle was analyzed using flow cytometry. Temozolomide (TMZ)-resistant glioma cells were established to define the effect of NR5A2 on drug resistance. The expressions of Notch pathway-related proteins were assessed by Western blot. Glioma nude mice model was constructed to explore the role of NR5A2 played in vivo.Results: NR5A2 was highly expressed in glioma tissues and cell lines. NR5A2 overexpression was related to the poor prognosis of glioma patients. NR5A2 knockdown inhibited cell viability, proliferation, migration, and invasion, induced cell cycle arrest and promoted cell apoptosis in U138 and U251 cells. In U138/TMZ and U251/TMZ cell lines, NR5A2 upregulation enhanced TMZ resistance while NR5A2 downregulation reduced it. The knockdown of NR5A2 influenced the expressions of Notch pathway-related proteins. NR5A2 knockdown suppressed tumor growth and facilitated apoptosis in glioma mice model.Conclusion: NR5A2 affected glioma cell malignant behaviors and TMZ resistance via Notch signaling pathway and it might be a novel target in glioma therapy.Keywords: glioma, Notch signaling pathway, temozolomide (TMZ), animal model, NR5A2
