ZNF740 facilitates the malignant progression of hepatocellular carcinoma via the METTL3/HIF‑1A signaling axis.

Abstract

Hepatocellular carcinoma (HCC) is the second leading cause of cancer‑related death, and efficient treatments to facilitate recovery and enhance long‑term outcomes are lacking. Zinc finger proteins (ZNFs), known as the largest group of transcription factors, have gained interest for their roles in HCC by stimulating the transcription of well‑known tumor‑causing genes. However, the specific roles and molecular mechanisms of ZNF740 in HCC remain unknown. The present study performed bioinformatics analysis and RNA‑sequencing analysis of differentially expressed genes in HCC, detected ZNF740 expression levels in HCC using reverse transcription‑quantitative PCR, western blotting and immunohistochemistry, and explored the effects of ZNF740 on the progression of liver cancer in vitro and in vivo using cellular functionality assays and cell‑derived xenografts. In addition, a dual‑luciferase reporter assay was performed to analyze the binding of ZNF740 with the METTL3 promoter. Furthermore, cell functionality experiments were performed to analyze whether ZNF740 promotes the proliferation of liver cancer cells in a METTL3‑dependent manner. Bioinformatics and immunoprecipitation assays were further used to analyze the molecular mechanism of ZNF740 in liver cancer. The present study demonstrated that ZNF740 expression was upregulated in HCC. Mechanistically, overexpressed ZNF740 interacted with the methyltransferase‑like 3 (METTL3) promoter and increased METTL3 expression, leading to the stabilization of hypoxia‑inducible factor‑1A (HIF1A) mRNA in an N6‑methyladenosine/YTH N6‑methyladenosine RNA‑binding protein 1‑dependent manner. Eventually, the ZNF740/METTL3/HIF1A signaling axis may facilitate the proliferation, invasion and metastasis of liver cancer via METTL3/HIF‑1A signaling. The present findings revealed the important role of ZNF740 and suggested a potential therapeutic approach that might improve clinical therapies for liver cancer.