The cancer/testis antigen HORMAD1 promotes gastric cancer progression by activating the NF-κB signaling pathway and inducing epithelial-mesenchymal transition

Geng Bian; Weiyu Li; Dabing Huang; Qi Zhang; Xiping Ding; Xiaodong Zang; Yingquan Ye; Jie Cao; Ping Li

The cancer/testis antigen HORMAD1 promotes gastric cancer progression by activating the NF-κB signaling pathway and inducing epithelial-mesenchymal transition

Am J Transl Res. 2023 Sep 15;15(9):5808-5825. eCollection 2023.

Authors

Geng Bian^{1

2}, Weiyu Li^{3

4}, Dabing Huang⁵, Qi Zhang⁶, Xiping Ding⁷, Xiaodong Zang⁸, Yingquan Ye^{1

2}, Jie Cao⁹, Ping Li^{1

2}

Affiliations

¹ Department of Chinese Integrative Medicine Oncology, The First Affiliated Hospital of Anhui Medical University Hefei 230022, Anhui, China.
² Department of Integrated Traditional Chinese and Western Medicine, Anhui Medical University Hefei 230022, Anhui, China.
³ National Clinical Research Center of Digestive Diseases Beijing 100050, China.
⁴ Liver Research Center, Beijing Key Laboratory of Translational Medicine in Liver Cirrhosis, Beijing Friendship Hospital, Capital Medical University Beijing 100050, China.
⁵ Department of Oncology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China Hefei 230001, Anhui, China.
⁶ Department of Urology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China Hefei 230001, Anhui, China.
⁷ Department of Geriatrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China Hefei 230001, Anhui, China.
⁸ Department of Pediatrics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China Hefei 230001, Anhui, China.
⁹ Department of Respiratory, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China Hefei 230001, Anhui, China.

PMID: 37854207
PMCID: PMC10579032

Abstract

Objectives: HORMAD1 is a cancer/testis antigen (CTAs) that regulates DNA homologous recombination, mismatch repair, and other tumor characteristics. However, its role and regulatory mechanisms in gastric cancer remain unclear.

Methods: We performed transcriptomic profiling on seven gastric cancers and paired tissues; HORMAD1 was significantly upregulated in gastric cancer samples and was related to poor prognosis survival. Furthermore, cancer pathway microarray, bioinformatic analysis, western blot, and immunochemistry assay demonstrated that HORMAD1 affected the NF-κB signaling pathway.

Results: In vitro and vivo studies confirmed that HORMAD1 knockdown inhibited cell growth and invasion, whereas overexpression reversed these effects. Mechanistically, HORMAD1 regulates the epithelial-mesenchymal transition process (EMT) via the NF-κB pathway by increasing the phosphorylation levels of NF-κB (p-65) and Iκκ-β. Downstream target genes of the NF-κB signaling pathway, such as c-Myc, CyclinD1, may be involved in HORMAD1-induced tumorigenesis in gastric cancer (GC).

Conclusions: HORMAD1 plays an important role in gastric cancer progression and could be a promising prognostic biomarker and therapeutic target.

Keywords: HORMAD1; NF-κB signaling pathway; cell proliferation; gastric cancer; migration and invasion.