Down-Regulation of CIDEA Promoted Tumor Growth and Contributed to Cisplatin Resistance by Regulating the JNK-p21/Bad Signaling Pathways in Esophageal Squamous Cell Carcinoma

Frontiers in Oncology

Ya-Ping Gao¹  Jie Yan¹  Yong-Xu Jia¹  Yan-Ru Qin¹  Zhi-Wei Chang¹  Xiao-Xia Hou²  Lei Li³  Xin-Yuan Guan³ 

[1] Department of Clinical Oncology, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, China;Department of Clinical Oncology, The Third Peoples Hospital of Zhengzhou, Zhengzhou, China;Department of Clinical Oncology, The University of Hong Kong, Hong Kong, China;

关键词: esophageal squamous cell carcinoma;    cell death inducing DFF like effector A;    methylation;    cisplatin;    apoptosis;   

DOI  :  10.3389/fonc.2020.627845

来源: DOAJ

【 摘 要 】

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies with poor prognosis and lack of effective targeted therapies. In this study, we investigated the tumor suppressive role of the cell death inducing DFF like effector A (CIDEA) in ESCC. Firstly, public datasets and ESCC tissue microarray analysis showed that CIDEA was frequently down-regulated at both the mRNA and protein level. This was significantly associated with low differentiation and TNM stage in ESCC, and indicated poor prognosis for ESCC patients. Bisulfite genomic sequencing (BGS) and methylation-specific PCR (MSP) analysis revealed that the down-regulation of CIDEA was associated with hypermethylation of its promoter, which was also correlated with the poor prognosis in ESCC patients. In vitro and in vivo functional studies demonstrated that CIDEA decreased cell growth, foci formation, DNA replication, and tumorigenesis in nude mice. Further study revealed that, during starvation or cisplatin induced DNA damage, CIDEA facilitated the G1-phase arrest or caspase-dependent mitochondrial apoptosis through the JNK-p21/Bad pathway. Therefore, CIDEA is a novel tumor suppressor gene that plays an important role in the development and progression of ESCC, and may provide a potential therapeutic target for patients with ESCC.

【 授权许可】

Unknown