E74‐like factor 4 promotes the proliferation, invasion, and migration of colorectal cancer cells via long non‐coding RNA integrin subunit beta 8 antisense RNA 1‐mediated histone H3 lysine 27 trimethylation modification

Abstract Aim Colorectal cancer (CRC) is a common malignancy in the gastrointestinal tract. The main objective of this study is to explore the potential mechanisms of E74‐like factor 4 (ELF4) in CRC progression, providing a novel therapeutic target for CRC treatment. Methods CRC cells and normal control cells were cultured. Levels of ELF4/long non‐coding RNA integrin subunit beta 8 antisense RNA 1 (LncRNA ITGB8‐AS1)/claudin‐23 (CLDN23) were detected by real‐time quantitative polymerase chain reaction or Western blot assay. ELF4 siRNA, ITGB8‐AS1 pcDNA3.1, or CLDN23 siRNA were transfected into cells. Cell proliferation, migration, and invasion were evaluated. The enrichment of ELF4 on the ITGB8‐AS1 promoter was detected. Dual‐luciferase assay was employed to assess the binding between ELF4 and the ITGB8‐AS1 promoter. RNA pull‐down and RNA immunoprecipitation assays were conducted to investigate the binding between ITGB8‐AS1 and enhancer of zeste homolog 2 (EZH2). The binding of EZH2 and histone H3 lysine 27 trimethylation (H3K27me3) to the CLDN23 promoter was detected. Results ELF4 and ITGB8‐AS1 were upregulated in CRC cells, while CLDN23 was downregulated. Knockdown of ELF4 inhibited cell proliferation, invasion, and migration. Mechanistically, ELF4 transcriptionally activated ITGB8‐AS1 and promoted the binding between ITGB8‐AS1 and EZH2. EZH2 catalyzed H3K27me3 modification on the CLDN23 promoter, leading to decreased CLDN23 expression. Overexpression of ITGB8‐AS1 or downregulation of CLDN23 could reduce the inhibitory effects of silencing ELF4 on CRC cell proliferation, migration, and invasion. Conclusion ELF4 accelerates CRC progression through the ITGB8‐AS1/CLDN23 axis, providing new therapeutic targets for CRC.