The Deubiquitinase USP39 Promotes Esophageal Squamous Cell Carcinoma Malignancy as a Splicing Factor

Xiaolin Zhu; Jianlin Ma; Minyi Lu; Zhihua Liu; Yongkun Sun; Hongyan Chen

doi:10.3390/genes13050819

The Deubiquitinase USP39 Promotes Esophageal Squamous Cell Carcinoma Malignancy as a Splicing Factor

Genes (Basel). 2022 May 3;13(5):819. doi: 10.3390/genes13050819.

Authors

Xiaolin Zhu¹, Jianlin Ma¹, Minyi Lu¹, Zhihua Liu¹, Yongkun Sun^{2

3}, Hongyan Chen¹

Affiliations

¹ State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
² Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/ Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
³ Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Hebei Cancer Hospital, Chinese Academy of Medical Sciences, Langfang 065001, China.

Abstract

Esophageal squamous cell carcinoma (ESCC) is an aggressive epithelial malignancy and the underlying molecular mechanisms remain elusive. Here, we identify that the ubiquitin-specific protease 39 (USP39) drives cell growth and chemoresistance by functional screening in ESCC, and that high expression of USP39 correlates with shorter overall survival and progression-free survival. Mechanistically, we provide evidence for the role of USP39 in alternative splicing regulation. USP39 interacts with several spliceosome components. Integrated analysis of RNA-seq and RIP-seq reveals that USP39 regulates the alternative splicing events. Taken together, our results indicate that USP39 functions as an oncogenic splicing factor and acts as a potential therapeutic target for ESCC.

Keywords: ESCC; USP39; splicing factor.

Publication types

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

MeSH terms

Cell Line, Tumor
Esophageal Neoplasms* / genetics
Esophageal Squamous Cell Carcinoma* / genetics
Humans
RNA Splicing Factors / genetics
Ubiquitin-Specific Proteases / genetics
Ubiquitin-Specific Proteases / metabolism

Substances

RNA Splicing Factors
USP39 protein, human
Ubiquitin-Specific Proteases

Grants and funding

This study was supported by the National Natural Science Foundation of China (82072756), the CAMS Innovation Fund for Medical Sciences (2021-I2M-1-067), the fund of the “San-ming” Project of Medicine in Shenzhen (SZSM201812062), and Guangdong Basic and Applied Basic Research Foundation (2019B030302012).