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

IF 1.4 4区医学 Q4 ONCOLOGY

Asia-Pacific journal of clinical oncology Pub Date : 2024-09-26 DOI:10.1111/ajco.14112

Qi Wang, Shaofeng Liu

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引用次数: 0

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.

查看原文本刊更多论文

E74 样因子 4 通过长非编码 RNA 整合素亚基 beta 8 反义 RNA 1 介导的组蛋白 H3 赖氨酸 27 三甲基化修饰促进结直肠癌细胞的增殖、侵袭和迁移。

目的：结直肠癌（CRC）是胃肠道常见的恶性肿瘤。本研究的主要目的是探索 E74 样因子 4（ELF4）在 CRC 进展中的潜在机制，为 CRC 治疗提供新的治疗靶点：方法：培养 CRC 细胞和正常对照细胞。通过实时定量聚合酶链反应或 Western 印迹检测 ELF4/长非编码 RNA 整合素亚基 beta 8 反义 RNA 1（LncRNA ITGB8-AS1）/claudin-23（CLDN23）的水平。将 ELF4 siRNA、ITGB8-AS1 pcDNA3.1 或 CLDN23 siRNA 转染到细胞中。对细胞增殖、迁移和侵袭进行评估。检测了 ELF4 在 ITGB8-AS1 启动子上的富集。采用双荧光素酶检测法评估 ELF4 与 ITGB8-AS1 启动子之间的结合。通过RNA牵引和RNA免疫沉淀实验研究了ITGB8-AS1与zeste同源增强子2（EZH2）之间的结合。检测了EZH2和组蛋白H3赖氨酸27三甲基化（H3K27me3）与CLDN23启动子的结合情况：结果：ELF4和ITGB8-AS1在CRC细胞中上调，而CLDN23下调。敲除ELF4可抑制细胞增殖、侵袭和迁移。从机理上讲，ELF4可转录激活ITGB8-AS1，并促进ITGB8-AS1与EZH2的结合。EZH2催化了CLDN23启动子上的H3K27me3修饰，导致CLDN23表达下降。ITGB8-AS1的过表达或CLDN23的下调可降低沉默ELF4对CRC细胞增殖、迁移和侵袭的抑制作用：ELF4通过ITGB8-AS1/CLDN23轴加速了CRC的进展，为CRC提供了新的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Asia-Pacific journal of clinical oncology 医学-肿瘤学

CiteScore

3.40

自引率

0.00%

发文量

175

审稿时长

6-12 weeks

期刊介绍： Asia–Pacific Journal of Clinical Oncology is a multidisciplinary journal of oncology that aims to be a forum for facilitating collaboration and exchanging information on what is happening in different countries of the Asia–Pacific region in relation to cancer treatment and care. The Journal is ideally positioned to receive publications that deal with diversity in cancer behavior, management and outcome related to ethnic, cultural, economic and other differences between populations. In addition to original articles, the Journal publishes reviews, editorials, letters to the Editor and short communications. Case reports are generally not considered for publication, only exceptional papers in which Editors find extraordinary oncological value may be considered for review. The Journal encourages clinical studies, particularly prospectively designed clinical trials.