<p><em>NR5A2</em> Promotes Cell Growth and Resistance to Temozolomide Through Regulating Notch Signal Pathway in Glioma</p>

Abstract

Background: 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 downexpressed 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.

Identification of tumor antigens and immune subtypes of glioma for mRNA vaccine development

“…Further studies showed that NR5A2 could promote cell proliferation and tumor growth via Notch signaling pathway, suggesting that it might be a novel target for immunotherapy in glioma. 33 Besides, BRCA2 was essential for homologous recombination (HR)‐dependent double‐strand break (DSB) repairing pathway and thus participated in glioma resistance to alkylating agents. Therefore, targeting BRCA2 might be a useful strategy to increase sensitivity to alkylating anticancer drugs.…”

“…Yang et al, for example, found that NR5A2 was highly expressed in glioma tissues and cell lines, and its overexpression was associated with poor prognosis of glioma patients. Further studies showed that NR5A2 could promote cell proliferation and tumor growth via Notch signaling pathway, suggesting that it might be a novel target for immunotherapy in glioma 33 . Besides, BRCA2 was essential for homologous recombination (HR)‐dependent double‐strand break (DSB) repairing pathway and thus participated in glioma resistance to alkylating agents.…”

Triptolide reverses epithelial-mesenchymal transition in glioma cells via inducing autophagy

“…This is a profound platform that can be utilized to analyze the current and future trends in the diagnosis and prognosis of glioma from molecular biology to proteomics. Recent studies disclosed several signal pathways that closely related to the proliferation and metastasis of glioma, such as IGF-1R/AKT, Notch, mTOR, Wnt and EMT (28)(29)(30)(31)(32). EMT is an indispensable part of the normal development process of the human body, and it also plays a crucial role in tumor progression and metastasis.…”

Purple sweet potato delphinidin-3-rutin represses glioma proliferation by inducing miR-20b-5p/Atg7-dependent cytostatic autophagy

“…Data were examined with FlowJo software. 55 Transfection of plasmids, mimic, inhibitors, and LV constructs miR-20b-5p mimic (20b-5p-m; used for overexpression of miR-20b-5p); NS-m (negative control of 20b-5p-m); 20b-5p-in (used for inhibiting expression of miR-20b-5p); NS-in (negative control of 20b-5pin); sh-Creb plasmids (used for inhibiting expression of Creb); negative control of shRNA plasmids (sh-NC; negative control of sh-Creb); overexpressed Creb plasmids (oe-Creb; used for overexpression of Creb); empty vector (vector; negative control of oe-Creb); CA-Akt (used for constitutively expression of active Akt); green and red fluorescence protein-tagged LC3 plasmid (LC3-GFP-RFP; used for expression of LC3 with fluorescence); and pcDNA3.1 plasmids (empty vector; negative control of LC3-GFP-RFP) were obtained from Sangon Biotech. LV miR-20b-5p inhibition construct (LV-20b-5p-in; used for inhibiting expression of miR-20b-5p) and LV-C were obtained from Shanghai Genechem (Shanghai, China).…”