Knockdown of TRIM32 inhibits tumor growth and increases the therapeutic sensitivity to temozolomide in glioma in a p53-dependent and -independent manner

Yu Cai; Wei Ting Gu; Kang Cheng; Pei Feng Jia; Feng Li; Ming Wang; Wei Feng Zhang; Ji Ting Qiu; Zhe Bao Wu; Wei Guo Zhao

doi:10.1016/j.bbrc.2021.02.098

Knockdown of TRIM32 inhibits tumor growth and increases the therapeutic sensitivity to temozolomide in glioma in a p53-dependent and -independent manner

Biochem Biophys Res Commun. 2021 Apr 23:550:134-141. doi: 10.1016/j.bbrc.2021.02.098. Epub 2021 Mar 7.

Authors

Yu Cai¹, Wei Ting Gu¹, Kang Cheng², Pei Feng Jia², Feng Li², Ming Wang², Wei Feng Zhang², Ji Ting Qiu², Zhe Bao Wu³, Wei Guo Zhao⁴

Affiliations

¹ Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China; Department of Neurosurgery, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
² Department of Neurosurgery, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
³ Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China.
⁴ Department of Neurosurgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Electronic address: ruijinzhaoweiguo@163.com.

PMID: 33691199
DOI: 10.1016/j.bbrc.2021.02.098

Abstract

Tripartite motif protein 32 (TRIM32), an E3 ubiquitin ligase, has been reported to participate in many human cancers. However, the underlying role of TRIM32 in glioma remains largely unknown. Here, we aimed to explore the function of TRIM32 in glioma cells and the clinical implications and found that TRIM32 was upregulated in glioma tissues. Consistently, overexpression of TRIM32 promoted glioma U87 and U251 cell proliferation and conferred cell resistance to temozolomide (TMZ). Conversely, knockdown of TRIM32 inhibited glioma cells proliferation in vitro and in vivo and sensitized glioma cells to the treatment of TMZ in a p53-dependent and -independent manner. Mechanistically, knockdown of TRIM32 induced apoptosis of U87 an U251 cells. In addition, TRIM32 interacted with the antiapoptotic proteins BCL-xL and BCL-w, which antagonized the inhibitory effect of TRIM32 knockdown in U87 cells. Together, our study uncovered the role of TRIM32 in glioma and TRIM32 may be a potential therapeutic target for gliomas.

Keywords: Cell proliferation; Glioma; TRIM32; Temozolomide; Therapeutic resistance.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects
Apoptosis / genetics
Apoptosis Regulatory Proteins / biosynthesis
Apoptosis Regulatory Proteins / genetics
Cell Line, Tumor
Cell Proliferation*
Drug Resistance, Neoplasm* / genetics
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Glioma / drug therapy*
Glioma / genetics
Glioma / pathology*
Humans
Mice
Molecular Targeted Therapy
Neoplasm Grading
Temozolomide / pharmacology
Temozolomide / therapeutic use*
Transcription Factors / biosynthesis
Transcription Factors / deficiency*
Transcription Factors / genetics
Transcription Factors / metabolism
Tripartite Motif Proteins / biosynthesis
Tripartite Motif Proteins / deficiency*
Tripartite Motif Proteins / genetics
Tripartite Motif Proteins / metabolism
Tumor Suppressor Protein p53* / biosynthesis
Tumor Suppressor Protein p53* / deficiency
Tumor Suppressor Protein p53* / genetics
Tumor Suppressor Protein p53* / metabolism
Ubiquitin-Protein Ligases / biosynthesis
Ubiquitin-Protein Ligases / deficiency*
Ubiquitin-Protein Ligases / genetics
Ubiquitin-Protein Ligases / metabolism
Up-Regulation
Xenograft Model Antitumor Assays

Substances

Apoptosis Regulatory Proteins
TP53 protein, human
Transcription Factors
Tripartite Motif Proteins
Tumor Suppressor Protein p53
TRIM32 protein, human
Ubiquitin-Protein Ligases
Temozolomide