Upregulation of ADAR Promotes Breast Cancer Progression and Serves as a Potential Therapeutic Target

Xiao Li; Guangshun Sun; Liangliang Wu; Guoqiang Sun; Ye Cheng; Jing Tao; Zhouxiao Li; Weiwei Tang; Hanjin Wang

doi:10.1155/2021/2012903

Upregulation of ADAR Promotes Breast Cancer Progression and Serves as a Potential Therapeutic Target

J Oncol. 2021 Sep 27:2021:2012903. doi: 10.1155/2021/2012903. eCollection 2021.

Authors

Xiao Li¹, Guangshun Sun¹, Liangliang Wu¹, Guoqiang Sun¹, Ye Cheng², Jing Tao³, Zhouxiao Li⁴, Weiwei Tang⁵, Hanjin Wang¹

Affiliations

¹ Department of General Surgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.
² Department of General Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.
³ Department of General Surgery, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, Jiangsu, China.
⁴ Department of Hand Surgery, Plastic Surgery and Aesthetic Surgery, Ludwig-Maximilians University, Munich, Germany.
⁵ Hepatobiliary/Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Transplantation, Chinese Academy of Medical Sciences, Nanjing, Jiangsu, China.

Abstract

Background: Breast cancer (BC) is the most common cause of cancer death worldwide, and its incidence is increasing every year. This study aims to investigate the expression characteristics of ADAR gene in breast cancer and to explore its role in the occurrence and development of BC and its possible mechanism.

Methods: TCGA portal was used to detect the expression of ADAR in cancer including BC, and its correlation with clinicopathological data as well as other genes was analyzed via UALCAN database. The TISCH database evaluated the expression of ADAR in different types of cell populations in BC at the single-cell level. The Kaplan-Meier plotter database was used to predict the correlation between ADAR expression and BC patient prognosis. The Human Protein Atlas was used to detect the expression of ADAR in tissues and location of ADAR mRNA in cells. Moreover, the relationships between immune response and ADAR expression in BC were assessed with the use of the TISIDB. Metascape and STRING were applied to predict ADAR with other protein interactions. Finally, the effect generated by ADAR expression on cell proliferating, invading, and migrating processes was assessed in vitro with knockdown and overexpression strategies.

Results: ADAR was significantly upregulated in BC tissues compared to paracancerous tissues. Single-cell RNA analysis showed that ADAR was specifically upregulated in cancer cell clusters and was also expressed in stromal and immune cell clusters. The upregulation of ADAR was positively correlated with clinicopathological stage and negatively correlated with BC prognosis. Experimental processes in vitro revealed ADAR knockdown hindered, proliferated, invaded, and migrated levels of BC cells, whereas over expression of ADAR played the opposite effect. ADAR protein, which may interact with OASL, STAT2, and IFIT3, was mainly located in the nucleoli in cells and primarily involved DNA modification and apoptotic signaling pathway. Immune factors may interact with ADAR in BC, and ADAR was found noticeably linked with immunosuppressor such as IL10, CD274, and IDO1.

Conclusion: ADAR is significantly upregulated in breast cancer tissues, which may promote the progression of BC through the interaction of cancer cells, stromal cells, and immune cells. Targeting ADAR may offer new hope in treating breast cancer.