Cheng Yu-Wen, Lee Jia-Hau, Chang Chih-Hui, Tseng Tzu-Ting, Chai Chee-Yin, Lieu Ann-Shung, Kwan Aij-Lie
Department of Neurosurgery, Kaohsiung Veterans General Hospital, Kaohsiung 807, Taiwan.
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Biomedicines. 2024 Apr 29;12(5):979. doi: 10.3390/biomedicines12050979.
Gliomas are the most common primary brain tumors in adults. Despite multidisciplinary treatment approaches, the survival rates for patients with malignant glioma have only improved marginally, and few prognostic biomarkers have been identified. Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) is a crucial regulator of cancer metabolism, playing a vital role in cancer cell adaptation to fluctuating energy demands. In this study, the clinicopathological roles of PGC-1α in gliomas were evaluated. Employing immunohistochemistry, cell culture, siRNA transfection, cell viability assays, western blot analyses, and in vitro and in vivo invasion and migration assays, we explored the functions of PGC-1α in glioma progression. High PGC-1α expression was significantly associated with an advanced pathological stage in patients with glioma and with poorer overall survival. The downregulation of PGC-1α inhibited glioma cell proliferation, invasion, and migration and altered the expression of oncogenic markers. These results conclusively demonstrated that PGC-1α plays a critical role in maintaining the malignant phenotype of glioma cells and indicated that targeting PGC-1α could be an effective strategy to curb glioma progression and improve patient survival outcomes.
胶质瘤是成人中最常见的原发性脑肿瘤。尽管采用了多学科治疗方法，但恶性胶质瘤患者的生存率仅略有提高，且几乎没有发现预后生物标志物。过氧化物酶体增殖物激活受体γ（PPARγ）共激活因子-1α（PGC-1α）是癌症代谢的关键调节因子，在癌细胞适应波动的能量需求中起着至关重要的作用。在本研究中，评估了PGC-1α在胶质瘤中的临床病理作用。通过免疫组织化学、细胞培养、小干扰RNA转染、细胞活力测定、蛋白质免疫印迹分析以及体外和体内侵袭与迁移试验，我们探究了PGC-1α在胶质瘤进展中的功能。PGC-1α高表达与胶质瘤患者的病理分期进展以及较差的总生存率显著相关。PGC-1α的下调抑制了胶质瘤细胞的增殖、侵袭和迁移，并改变了致癌标志物的表达。这些结果确凿地证明，PGC-1α在维持胶质瘤细胞的恶性表型中起关键作用，并表明靶向PGC-1α可能是抑制胶质瘤进展和改善患者生存结果的有效策略。
