IDO1 facilitates esophageal carcinoma progression by driving the direct binding of NF-κB and CXCL10

Wenjian Yao; Xiaohai Cui; Haodong Peng; Yongkang Zhang; Xiangbo Jia; Sen Wu; Jian Zhao

doi:10.1038/s41420-023-01689-3

IDO1 facilitates esophageal carcinoma progression by driving the direct binding of NF-κB and CXCL10

Cell Death Discov. 2023 Oct 31;9(1):403. doi: 10.1038/s41420-023-01689-3.

Authors

Wenjian Yao^#¹, Xiaohai Cui^#², Haodong Peng³, Yongkang Zhang³, Xiangbo Jia¹, Sen Wu⁴, Jian Zhao⁵

Affiliations

¹ Department of Thoracic Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, No.7 Weiwu Road, Zhengzhou, 450003, Henan province, China.
² Department of Thoracic Surgery, The first affiliated hospital of xi'an jiaotong university, No.277 Yanta West Road, Xi'an, 710061, Shanxi province, China.
³ Department of Thoracic Surgery, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, No.7 Weiwu Road, Zhengzhou, 45003, Henan province, China.
⁴ Department of Thoracic Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, No.7 Weiwu Road, Zhengzhou, 450003, Henan province, China. wusen1213@163.com.
⁵ Department of Thoracic Surgery, Liaoning Cancer Hospital, No.44-3 Xiaohe Yan Road, Dadong District, Shenyang, 110000, Liaoning Province, China. zj385606@163.com.

^# Contributed equally.

Abstract

Esophageal carcinoma (EC), one of the most lethal human malignancies, lacks effective targeted therapies. Indoleamine 2,3-dioxygenase 1 (IDO1) plays a key role in a variety of cancers, but its role and mechanism in EC are still unclear. Immunohistochemistry and qRT-PCR were used to analyze the expression of IDO1 in EC, and the prognostic value of IDO1 in EC was evaluated by Kaplan-Meier test. The in vitro and in vivo function loss/acquisition tests were performed to evaluate the biological effects of IDO1 in EC. The mechanism of action of IDO1-regulation EC was explored through Firefly luciferase & Renilla luciferase activity reporter, chromatin immunoprecipitation (ChIP) and immunofluorescence (IF) assays. Clinically, IDO1 expression was abnormally elevated in EC and positively correlated with overall survival. Functionally, IDO1 was contributed to the proliferation and migration of EC cells. Mechanically, IDO1 regulated the expression of chemokine C-X-C ligand 10 (CXCL10) by promoting the entry of NF-κB into the nucleus to combine with the promoter of CXCL10. Consistently, IDO1 facilitated EC progression may dependent on the presence of CXCL10. Moreover, NF-κB alleviated the inhibitory effect of IDO1 knockdown on EC. IDO1 drove the progression of EC by directly binding NF-κB and CXCL10, the finding that may provide an effective theoretical basis for precise therapies for EC.