Long non-coding RNA FOXP4-AS1 facilitates the biological functions of hepatocellular carcinoma cells via downregulating ZC3H12D by mediating H3K27me3 through recruitment of EZH2,Cell Biology and Toxicology

当前位置： X-MOL 学术 › Cell Biol. Toxicol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Long non-coding RNA FOXP4-AS1 facilitates the biological functions of hepatocellular carcinoma cells via downregulating ZC3H12D by mediating H3K27me3 through recruitment of EZH2
Cell Biology and Toxicology ( IF 5.3 ) Pub Date : 2021-09-21 , DOI: 10.1007/s10565-021-09642-9
Junfeng Ye ₁ , Yu Fu ₁ , Zhongfeng Wang ₂ , Jinhai Yu ₃

Affiliation

Background

Some studies have reported the effect of long non-coding RNA forkhead box P4 antisense RNA 1 (lncRNA FOXP4-AS1) on hepatocellular carcinoma (HCC). Here, we aimed to discuss the effects of FOXP4-AS1/enhancer of zeste homolog 2 (EZH2)/trimethylation of lysine 27 on histone H3 (H3K27me3)/zinc finger CCCH-type containing 12D (ZC3H12D) axis on HCC.

Methods

The expression of FOXP4-AS1, EZH2, and ZC3H12D, and abundance of H3K27me3 in HCC tissues and cells were tested. The relationship between FOXP4-AS1 expression and prognosis of HCC patients was analyzed. The biological functions of HCC cells were detected via loss- and gain-of-function assays. The tumor weight and volume in vivo were tested. The interaction between FOXP4-AS1 and EZH2 as well as that between EZH2 and H3K27me3 was verified.

Results

FOXP4-AS1 and EZH2 expression and H3K27me3 abundance were enhanced while ZC3H12D expression was depressed in HCC tissues and cells. Knockdown of FOXP4-AS1 suppressed biological functions of HCC cells as well as the weight and volume of HCC transplanted tumor. Depleting ZC3H12D reversed the effect of downregulated FOXP4-AS1 on HCC cells. FOXP4-AS1 suppressed ZC3H12D expression via mediating H3K27me3 by recruitment of EZH2.

Conclusion

The key findings of the present study demonstrate that FOXP4-AS1 suppresses ZC3H12D expression via mediating H3K27me3 by recruitment of EZH2, thus promoting the progression of HCC.

Graphical abstract

中文翻译：

长链非编码 RNA FOXP4-AS1 通过募集 EZH2 介导 H3K27me3 下调 ZC3H12D 促进肝癌细胞的生物学功能

背景

一些研究报道了长链非编码 RNA 叉头盒 P4 反义 RNA 1 (lncRNA FOXP4-AS1) 对肝细胞癌 (HCC) 的影响。在这里，我们旨在讨论 FOXP4-AS1/zeste 同系物 2 (EZH2) 增强子/赖氨酸 27 三甲基化对组蛋白 H3 (H3K27me3)/含 12D (ZC3H12D) 轴的锌指 CCCH 型对 HCC 的影响。

方法

检测了 HCC 组织和细胞中 FOXP4-AS1、EZH2 和 ZC3H12D 的表达以及 H3K27me3 的丰度。分析FOXP4-AS1表达与HCC患者预后的关系。通过功能丧失和功能获得测定检测 HCC 细胞的生物学功能。测试体内肿瘤重量和体积。验证了 FOXP4-AS1 和 EZH2 之间以及 EZH2 和 H3K27me3 之间的相互作用。

结果

FOXP4-AS1 和 EZH2 表达和 H3K27me3 丰度增强，而 ZC3H12D 表达在 HCC 组织和细胞中被抑制。FOXP4-AS1 的敲低抑制了 HCC 细胞的生物学功能以及 HCC 移植肿瘤的重量和体积。耗尽 ZC3H12D 逆转了下调的 FOXP4-AS1 对 HCC 细胞的影响。FOXP4-AS1 通过募集 EZH2 介导 H3K27me3 来抑制 ZC3H12D 表达。