CLEC4D as a Novel Prognostic Marker Boosts the Proliferation and Migration of Gastric Cancer via the NF-κB/AKT Signaling Pathway

Abstract

Yang Yang,1– 5,* Mengmeng Zhang,1,3,5,* Fenglin Cai,6 Gang Ma,1,3,5 Ru-Peng Zhang,1,3,5 Yiqing Yin,2,4,5 Jingyu Deng1,3,5 1Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China; 2Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China; 3Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, People’s Republic of China; 4Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, People’s Republic of China; 5Tianjin’s Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China; 6Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, 300070, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yiqing Yin, Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, West Huan-Hu Road, Ti Yuan Bei, Hexi District, Tianjin, 300060, People’s Republic of China, Email [email protected] Jingyu Deng, Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, People’s Republic of China, Email [email protected]: The functions of C-type lectin domain family 4 member D (CLEC4D), one member of the C-type lectin/C-type lectin-like domain superfamily, in immunity have been well described, but its roles in cancer biology remain largely unknown.Patients and Methods: This study aims to explore the role of CLEC4D in gastric cancer (GC). Bioinformatics preliminarily analyzed the expression of CLEC4D in gastric cancer. Immunohistochemical staining was used to detect the expression level and clinical pathological characteristics of CLEC4D in gastric cancer. The biological function of CLEC4D in gastric cancer cell lines was verified through in vitro and in vivo experiments.Results: In this study, CLEC4D expression was found to be markedly increased in gastric cancer (GC) tissues compared with matched normal gastric tissues, and high CLEC4D expression independently predicted unfavorable overall survival in patients with GC. Knockdown of CLEC4D markedly inhibited GC cell proliferation and migration. Mechanistically, CLEC4D knockdown deactivated the Akt and NF-κB signaling pathways in GC cells.Conclusion: Together, these results demonstrate that aberrantly increased CLEC4D expression promotes cancer phenotypes via the Akt and NF-κB signaling pathways in GC cells.Keywords: CLEC4D, gastric cancer, NF-κB signaling pathways, migration

Keywords

• clec4d
• gastric cancer
• nf-κb signaling pathways
• migration.