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DNMT3L通过CDO1的DNA甲基化抑制肝细胞癌进展:从大数据到基础研究的见解

DNMT3L inhibits hepatocellular carcinoma progression through DNA methylation of CDO1: insights from big data to basic research.

作者信息

Yan Xiaokai, Qi Yao, Yao Xinyue, Zhou Nanjing, Ye Xinxin, Chen Xing

机构信息

Department of Oncology, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, China.

Shanghai Molecular Medicine Engineering Technology Research Center, Shanghai, 201203, China.

出版信息

J Transl Med. 2024 Feb 2;22(1):128. doi: 10.1186/s12967-024-04939-9.

Abstract

BACKGROUND

DNMT3L is a crucial DNA methylation regulatory factor, yet its function and mechanism in hepatocellular carcinoma (HCC) remain poorly understood. Bioinformatics-based big data analysis has increasingly gained significance in cancer research. Therefore, this study aims to elucidate the role of DNMT3L in HCC by integrating big data analysis with experimental validation.

METHODS

Dozens of HCC datasets were collected to analyze the expression of DNMT3L and its relationship with prognostic indicators, and were used for molecular regulatory relationship evaluation. The effects of DNMT3L on the malignant phenotypes of hepatoma cells were confirmed in vitro and in vivo. The regulatory mechanisms of DNMT3L were explored through MSP, western blot, and dual-luciferase assays.

RESULTS

DNMT3L was found to be downregulated in HCC tissues and associated with better prognosis. Overexpression of DNMT3L inhibits cell proliferation and metastasis. Additionally, CDO1 was identified as a target gene of DNMT3L and also exhibits anti-cancer effects. DNMT3L upregulates CDO1 expression by competitively inhibiting DNMT3A-mediated methylation of CDO1 promoter.

CONCLUSIONS

Our study revealed the role and epi-transcriptomic regulatory mechanism of DNMT3L in HCC, and underscored the essential role and applicability of big data analysis in elucidating complex biological processes.

摘要

背景

DNMT3L是一种关键的DNA甲基化调节因子,但其在肝细胞癌(HCC)中的功能和机制仍知之甚少。基于生物信息学的大数据分析在癌症研究中日益重要。因此,本研究旨在通过将大数据分析与实验验证相结合,阐明DNMT3L在HCC中的作用。

方法

收集数十个HCC数据集,分析DNMT3L的表达及其与预后指标的关系,并用于分子调控关系评估。在体外和体内证实了DNMT3L对肝癌细胞恶性表型的影响。通过甲基化特异性PCR(MSP)、蛋白质免疫印迹法和双荧光素酶测定法探索DNMT3L的调控机制。

结果

发现DNMT3L在HCC组织中表达下调,且与较好的预后相关。DNMT3L的过表达抑制细胞增殖和转移。此外,CDO1被鉴定为DNMT3L的靶基因,也具有抗癌作用。DNMT3L通过竞争性抑制DNMT3A介导的CDO1启动子甲基化来上调CDO1表达。

结论

我们的研究揭示了DNMT3L在HCC中的作用和表观转录组调控机制,并强调了大数据分析在阐明复杂生物学过程中的重要作用和适用性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc59/10837993/d36604b91c33/12967_2024_4939_Fig1_HTML.jpg

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