Zhao Zhipeng, Wang Yuqi, Yun Dapeng, Huang Qilin, Meng Delong, Li Qing, Zhang Pingzhao, Wang Chenji, Chen Hongyan, Lu Daru
State Key Laboratory of Genetic Engineering and MOE Engineering Research Center of Gene Technology, School of Life Sciences, Fudan University Shanghai 200438, China.
School of Physical Education, Xizang Minzu University Xianyang 712000, Shaanxi, China.
Am J Cancer Res. 2020 Jan 1;10(1):114-130. eCollection 2020.
Molecular biomarkers combined with histopathological examination are of critical importance in the diagnosis and treatment of gliomas. Although recent studies have shown that many tripartite motif-containing (TRIM) family proteins could regulate the cell cycle, cell proliferation, and differentiation in cancers, the precise role of TRIM21 has been unknown in glioma. In this study, we analyzed TRIM21, which was upregulated in gliomas and identified its role in tumor proliferation, migration and drug resistance. By using immunohistochemical analysis, we found that the expression level of TRIM21 was upregulated in glioma specimens and the higher expression level of TRIM21 was associated with poorer clinical outcomes in glioma patients. Moreover, we demonstrated that TRIM21 could act as a regulator of the proliferation, cell cycle, and migration of glioma cells by gain- and loss-of function assays in vitro. In vivo, TRIM21 could also modulate glioma progression in murine intracranial xenografts. Furthermore, we found that TRIM21 suppressed cellular senescence via the p53-p21 pathway, and increased drug resistance in glioma cells by RNA-seq analysis, SA--Gal activity assay, and Cell Counting Kit-8 (CCK-8) assay. These results indicated that TRIM21 is a novel regulator in the diagnosis, prognosis, and therapy of gliomas.
分子生物标志物与组织病理学检查相结合在胶质瘤的诊断和治疗中至关重要。尽管最近的研究表明，许多含三联基序（TRIM）的家族蛋白可调节癌症中的细胞周期、细胞增殖和分化，但TRIM21在胶质瘤中的具体作用尚不清楚。在本研究中，我们分析了在胶质瘤中上调的TRIM21，并确定了其在肿瘤增殖、迁移和耐药性中的作用。通过免疫组织化学分析，我们发现TRIM21在胶质瘤标本中的表达水平上调，且TRIM21的高表达水平与胶质瘤患者较差的临床结局相关。此外，我们通过体外功能获得和功能丧失试验证明，TRIM21可作为胶质瘤细胞增殖、细胞周期和迁移的调节因子。在体内，TRIM21也可调节小鼠颅内异种移植瘤中的胶质瘤进展。此外，我们通过RNA测序分析、SA-β-Gal活性测定和细胞计数试剂盒-8（CCK-8）测定发现，TRIM21通过p53-p21途径抑制细胞衰老，并增加胶质瘤细胞的耐药性。这些结果表明，TRIM21是胶质瘤诊断、预后和治疗中的一种新型调节因子。
