Overexpression of ZNF468 promotes esophageal squamous cell carcinoma progression via the AKT/mTOR pathway

• Published in: International immunopharmacology Vol. 143; no. Pt 3; p. 113509
• Main Authors: Ye, Luxia, Pan, Yixiao, Bao, Jiaqian, Guo, Yiqing, Lu, Lingxiao, Zheng, Jingmin
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 25.12.2024
• Subjects: Esophageal squamous cell carcinoma; Invasion; Migration; Proliferation; ZNF468; PRAD; STAD; Migration; UCEC; Proliferation; ESCA; KIRC; Invasion; LUAD; PCPG; COAD; BRCA; GBM; THCA; BLCA; Esophageal squamous cell carcinoma; LUSC; LIHC; ZNF468; CHOL
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.113509

•ZNF468 was first studied in esophageal cancer.•Blocking ZNF468 may be an effective therapeutic strategy for ESCC.•Multiple pathways, including the AKT/mTOR pathway, may be involved in the function of ZNF468. ZNF468 is a zinc finger protein that plays a key role in the occurrence and development of tumors. However, no studies have demonstrated whether ZNF468 is involved in the progression of esophageal squamous cell carcinoma (ESCC). The expression of ZNF468 in ESCC tumor and normal samples was analyzed by the TCGA database and confirmed by tissue immunohistochemistry. Subsequently, we established the lentivirus ZNF468 knockdown and ZNF468 overexpression models using ESCC cell lines. The effect of ZNF468 on ESCC was assessed by in vivo and in vitro experiments. The latter included CCK8, colony formation, wound healing, and transwell assays. Additionally, we also explored the underlying mechanism. The mRNA and protein expression of ZNF468 were significantly increased in the tumor tissue of ESCC patients compared to normal para-cancerous tissue. Patients with high ZNF468 level were significantly related to shorter overall survival and disease-specific survival. Overexpression of ZNF468 increased the ability of proliferation, migration, and invasion of ESCC cells. In vivo experiments indicated that ZNF468 inhibition could also decrease the ESCC tumor growth. At last, we found that ZNF468 might affect ESCC progression through the AKT/mTOR signaling pathway. These findings showed that increased ZNF468 expression might promote ESCC progression via the AKT/mTOR pathway, which might be a potential biomarker and drug target for ESCC.