TRIM21 overexpression promotes tumor progression by regulating cell proliferation, cell migration and cell senescence in human glioma

Zhipeng Zhao; Yuqi Wang; Dapeng Yun; Qilin Huang; Delong Meng; Qing Li; Pingzhao Zhang; Chenji Wang; Hongyan Chen; Daru Lu

TRIM21 overexpression promotes tumor progression by regulating cell proliferation, cell migration and cell senescence in human glioma

Am J Cancer Res. 2020 Jan 1;10(1):114-130. eCollection 2020.

Authors

Zhipeng Zhao^{1

2}, Yuqi Wang¹, Dapeng Yun³, Qilin Huang⁴, Delong Meng⁵, Qing Li⁶, Pingzhao Zhang⁷, Chenji Wang⁸, Hongyan Chen¹, Daru Lu^{1

9}

Affiliations

¹ State Key Laboratory of Genetic Engineering and MOE Engineering Research Center of Gene Technology, School of Life Sciences, Fudan University Shanghai 200438, China.
² School of Physical Education, Xizang Minzu University Xianyang 712000, Shaanxi, China.
³ Department of Pharmacology, The University of Texas Southwestern Medical Center Dallas TX75390, USA.
⁴ Department of Neurosurgery, Shanghai Institute of Neurosurgery, Changzheng Hospital, Second Military Medical University Shanghai 200003, China.
⁵ Department of Molecular Biology, The University of Texas Southwestern Medical Center Dallas TX75390, USA.
⁶ Shanghai Center for Clinical Laboratory 528 Hongshan Road, Pudong District, Shanghai 200126, China.
⁷ Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences, Shanghai Medical College Shanghai 200032, China.
⁸ State Key Laboratory of Genetic Engineering, Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Fudan University Shanghai 200438, China.
⁹ Key Laboratory of Birth Defects and Reproductive Health of National Health and Family Planning Commission, Chongqing Population and Family Planning, Science and Technology Research Institute Chongqing 400020, China.

PMID: 32064156
PMCID: PMC7017742

Abstract

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-β-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.

Keywords: Glioma; TRIM21; cell senescence; drug resistance; p53-p21 pathway; prognosis.