DEPDC1B collaborates with GABRD to regulate ESCC progression

Yunfeng Yuan; Wei Ping; Ruijie Zhang; Zhipeng Hao; Ni Zhang

doi:10.1186/s12935-022-02593-z

DEPDC1B collaborates with GABRD to regulate ESCC progression

Cancer Cell Int. 2022 Jun 15;22(1):214. doi: 10.1186/s12935-022-02593-z.

Authors

Yunfeng Yuan¹, Wei Ping², Ruijie Zhang², Zhipeng Hao², Ni Zhang³

Affiliations

¹ Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200030, China.
² Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Wuhan, 430030, Hubei, China.
³ Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Wuhan, 430030, Hubei, China. zhangnidoc@vip.163.com.

Abstract

Background: Esophageal squamous cell carcinoma (ESCC) is the leading cause of cancer-related death worldwide with a poor prognosis. Given that DEPDC1B plays a key role in multiple cancers, the role of this molecule in ESCC was explored to identify potential targets for ESCC patients.

Method: The expression level of DEPDC1B in ESCC was revealed based on the TCGA database and immunohistochemical experiments on clinical tissues. The correlation between DEPDC1B and survival of ESCC patients was analyzed by Kaplan-Meier method. Small hairpin RNA (shRNA)-mediated silencing of DEPDC1B expression in ESCC cells and performed a series of in vitro and in vivo functional validations.

Result: DEPDC1B was overexpressed in ESCC. High expression of DEPDC1B was significantly negatively correlated with overall survival in patients with ESCC. Moreover, knockdown of DEPDC1B inhibited ESCC cell proliferation, clone formation, migration, tumor formation and promoted apoptosis. Furthermore, knockdown of DEPDC1B leaded to significant downregulation of GABRD in ESCC cells. Meanwhile, GABRD expression was upregulated in ESCC, and its silencing can inhibit the proliferation and migration of the tumor cells. Interestingly, there was a protein interaction between DEPDC1B and GABRD. Functionally, GABRD knockdown partially reversed the contribution of DEPDC1B to ESCC progression. In addition, GABRD regulated ESCC progression may depend on PI3K/AKT/mTOR signaling pathway.

Conclusion: DEPDC1B collaborated with GABRD to regulate ESCC progression, and inhibition of this signaling axis may be a potential therapeutic target for ESCC.

Keywords: DEPDC1B; ESCC; GABRD; Phenotype; Prognosis.