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

Yang Yang; Mengmeng Zhang; Fenglin Cai; Gang Ma; Ru-Peng Zhang; Yiqing Yin; Jingyu Deng

doi:10.2147/IJGM.S458228

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

Int J Gen Med. 2024 May 6:17:1923-1935. doi: 10.2147/IJGM.S458228. eCollection 2024.

Authors

Yang Yang^#^{1

2

3

4

5}, Mengmeng Zhang^#^{1

3

5}, Fenglin Cai⁶, Gang Ma^{1

3

5}, Ru-Peng Zhang^{1

3

5}, Yiqing Yin^{2

4

5}, Jingyu Deng^{1

3

5}

Affiliations

¹ Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China.
² Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China.
³ Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, People's Republic of China.
⁴ Tianjin Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, People's Republic of China.
⁵ Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, People's Republic of China.
⁶ Department of Biochemistry and Molecular Biology, Tianjin Medical University, Tianjin, 300070, People's Republic of China.

^# Contributed equally.

Abstract

Purpose: 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; NF-κB signaling pathways; gastric cancer; migration.

Grants and funding

This research was funded by Tianjin Key Medical Discipline (Specialty) Construction Project (TJYXZDXK-009A), National Key R&D Program of China (Grant No. 2016YFC1303200) and the Distinguished professor of Tianjin (JTZB [2019] No.120).