De-Ubiquitinating Enzymes USP21 Regulate MAPK1 Expression by Binding to Transcription Factor GATA3 to Regulate Tumor Growth and Cell Stemness of Gastric Cancer

Qingqu Guo; Dike Shi; Lele Lin; Hongbo Li; Yunhai Wei; Baozhong Li; Dan Wu

doi:10.3389/fcell.2021.641981

De-Ubiquitinating Enzymes USP21 Regulate MAPK1 Expression by Binding to Transcription Factor GATA3 to Regulate Tumor Growth and Cell Stemness of Gastric Cancer

Front Cell Dev Biol. 2021 Mar 15:9:641981. doi: 10.3389/fcell.2021.641981. eCollection 2021.

Authors

Qingqu Guo¹, Dike Shi¹, Lele Lin¹, Hongbo Li¹, Yunhai Wei², Baozhong Li³, Dan Wu¹

Affiliations

¹ Department of Gastrointestinal Surgery, The Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
² Department of Gastrointestinal Surgery, Huzhou Central Hospital, Huzhou, China.
³ Department of Surgery, Anyang Tumor Hospital, Anyang, China.

Abstract

USP21 is a kind of deubiquitinating enzymes involved in the malignant progression of various cancers, while its role in gastric cancer (GC) and the specific molecular mechanism are still unclear. This study probed into the function of USP21 in vitro and in vivo, and discussed the regulatory mechanism of USP21 in GC in vitro. We reported that USP21 promoted GC cell proliferation, migration, invasion, and stemness in vitro, and regulated GC tumor growth and cell stemness in mice in vivo. USP21 stabilized the expression of GATA3 by binding to GATA3. Besides, GATA3 also regulated the expression of MAPK1 at the transcriptional level. A series of in vitro experiments testified that USP21 regulated the expression of MAPK1 by binding to transcription factor GATA3, thereby regulating the tumor growth and cell stemness of GC. Overall, this study identified a new USP21/GATA3/MAPK1 axis, which plays a pivotal role in promoting the malignant progression of GC and might provide a potential target for treatment.

Keywords: GATA3; MAPK1; USP21; de-ubiquitination; gastric cancer; stemness.