Objective The role and mechanism of the CRYM gene in glioblastoma (GBM) remain unknown to date. Therefore, this study aims to report the abnormal expression of CRYM in glioblastoma and elucidate its function and underlying mechanism in GBM. Methods Using quantitative polymerase chain reaction (qRT-PCR) and western blotting(WB), we investigated the differential expression levels of CRYM between normal cells and various glioma cell lines, as well as between normal brain tissues and tumor tissues from patients with different grades of glioma. After overexpressing CRYM in various glioma cell lines via plasmid transfection, we demonstrated the role of CRYM in glioma cells through CCK-8, Transwell, wound healing, and EdU assays. The mechanism of CRYM in glioblastoma was elucidated using WB and a TGF beta 1 agonist. In animal in vivo experiments, we further revealed the inhibitory effect of CRYM overexpression on glioblastoma proliferation in nude mice via subcutaneous ectopic and intracranial orthotopic glioma transplantation models. Results The results demonstrated that CRYM expression was significantly downregulated in glioma cell lines compared to normal cell lines. Similarly, clinical glioma tissue samples exhibited lower CRYM levels than normal brain tissues, with expression decreasing progressively as glioma grade increased. Overexpression of CRYM markedly suppressed the proliferation and invasion of GBM cells in vitro. These findings were further corroborated by in vivo models, wherein CRYM overexpression significantly inhibited tumor growth in both subcutaneous ectopic and intracranial orthotopic xenograft assays. Bioinformatic analysis and WB revealed that CRYM exerts its tumor-suppressive effects primarily by inhibiting the TGF beta 1/Smad signaling pathway and epithelial-mesenchymal transition (EMT). Conclusion High expression of CRYM significantly suppresses GBM progression by inhibiting the TGF beta 1/Smad signaling pathway and EMT, suggesting CRYM as a potential therapeutic target for GBM. Furthermore, CRYM may also serve as a promising biomarker for the diagnosis and prognosis of GBM.
[1]Wannan Med Coll, Yijishan Hosp, Affiliated Hosp 1, Translat Res Inst Neurol Disorders,Dept Neurosurg, Wuhu 241001, Peoples R China.
[2]Southeast Univ, Xuzhou Cent Hosp, Canc Inst, Nanjing 210009, Peoples R China.
[3]Southeast Univ, Zhongda Hosp, Nanjing, Peoples R China.
[4]Southeast Univ, Adv Inst Life & Hlth, Nanjing, Peoples R China.
[5]Southeast Univ, Sch Med, Jiangsu Prov Key Lab Crit Care Med, Nanjing, Peoples R China.
(8.0+极速模式)