Journal of Hepatocellular Carcinoma (Sep 2024)
ZDHHC20 Activates AKT Signaling Pathway to Promote Cell Proliferation in Hepatocellular Carcinoma
Abstract
Xiaoju Huang,1– 3 Mengmeng Wang,1– 3 Dan Zhang,1– 3 Junpeng Meng,4,5 Pian Liu1– 3 1Cancer Center Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 2Hubei Key Laboratory of Precision Radiation Oncology, Wuhan, 430022, People’s Republic of China; 3Institute of Radiation Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 4Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People’s Republic of China; 5Department of General Surgery, the Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, 030001, People’s Republic of ChinaCorrespondence: Pian Liu; Junpeng Meng, Email [email protected]; [email protected]: Liver cancer is the sixth most common cancer worldwide, and hepatocellular carcinoma (HCC) presents one of the most challenging global health issues. ZDHHC20, a member of the ZDHHC palmitoyltransferase (ZDHHC-PAT) family, is involved in a reversible lipid modification known as palmitoylation, which contributes to the occurrence and progression of various tumors. However, the specific mechanisms underlying the involvement of ZDHHC20 in this process are unclear.Methods: The effects of both ZDHHC20 knockdown and overexpression on hepatocellular carcinoma cell proliferation were evaluated using PCR, Western blotting, CCK-8 assay, colony formation assay, cell cycle analysis, apoptosis analysis, and EDU assay. The TCGA-LIHC dataset was analyzed bioinformatically, and the phosphorylation level of PI3K and AKT in SK-Hep1 and Huh7 cells was assessed using Western blotting. Nude mouse subcutaneous xenograft experiments were conducted to evaluate the effects of different treatment conditions on mouse tumor growth.Results: ZDHHC20 knockdown inhibited cell proliferation and promoted apoptosis, while overexpression of ZDHHC20 promoted cell proliferation and inhibited apoptosis. Knockdown of ZDHHC20 also decreased phosphorylation of PI3K and AKT in HCC, whereas overexpression of ZDHHC20 increased phosphorylation of PI3K and AKT. The PI3K-AKT pathway inhibitors, LY294002 and MK2206, effectively inhibited the promotional effects of ZDHHC20 on the proliferation and growth of HCC.Conclusion: High expression of ZDHHC20 promotes the proliferation and tumor growth of HCC by activating the PI3K-AKT signaling pathway. The PI3K inhibitor LY294002 and the AKT inhibitor MK2206 inhibit the promotional effects of ZDHHC20 on the proliferation of HCC and the growth of tumors.Keywords: hepatocellular carcinoma, ZDHHC20, PI3K-AKT pathway, cell proliferation