Cancer-Type-Specific DNA Methylation Is a Source of Vulnerability in Liver Cancer Cells.

IF 5.7 2区医学 Q1 Medicine

Cancer Science Pub Date : 2025-05-02 DOI:10.1111/cas.70092

Karen Minowa, Miho Seki, Yui Nagai, Satoshi Yamashita

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引用次数: 0

Abstract

DNA methylation, a pivotal epigenetic mechanism, plays a critical role in various pathological conditions, including cancers. Notably, cancer-type-specific DNA methylation can be advantageous for survival only in specific environments while being disadvantageous in others. To investigate the role of cancer-type-specific methylation as a vulnerability in cancer cells, we bioinformatically profiled genome-wide DNA methylation in 1165 human cancer cell lines across 25 cancer types. The number of cancer-type-specific methylated cytosines varied significantly by organ, with exceptionally high numbers observed in blood cancers. A total of 73 genes were identified as potential liver cancer-specific methylation-silenced genes, and four genes, ASNS, NQO1, FXYD5, and BCAT2, were subjected to experimental further analysis. Silencing of BCAT2 was found to contribute to the vulnerability of liver cancer cells to BCAT1 inhibition by gabapentin. Additionally, the silencing of the other three genes also rendered liver cancer cells vulnerable under different environmental conditions. These findings enhance our understanding of the biological and clinical significance of DNA methylation and provide a basis for developing diagnostic markers for cancer. (169 words).

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癌症类型特异性DNA甲基化是肝癌细胞脆弱性的一个来源。

DNA甲基化是一种关键的表观遗传机制，在包括癌症在内的各种病理条件中起着关键作用。值得注意的是，癌症类型特异性DNA甲基化仅在特定环境中有利于生存，而在其他环境中则不利。为了研究癌症类型特异性甲基化在癌细胞中作为脆弱性的作用，我们对25种癌症类型的1165种人类癌细胞系的全基因组DNA甲基化进行了生物信息分析。癌症类型特异性甲基化胞嘧啶的数量因器官而异，在血癌中观察到异常高的数量。共有73个基因被鉴定为潜在的肝癌特异性甲基化沉默基因，并对ASNS、NQO1、FXYD5和BCAT2 4个基因进行实验进一步分析。BCAT2的沉默被发现有助于肝癌细胞对加巴喷丁抑制BCAT1的脆弱性。此外，其他三个基因的沉默也使肝癌细胞在不同的环境条件下变得脆弱。这些发现增强了我们对DNA甲基化的生物学和临床意义的认识，并为开发癌症诊断标志物提供了基础。(169字)。

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

Cancer Science ONCOLOGY-

CiteScore

9.90

自引率

3.50%

发文量

406

审稿时长

17 weeks

期刊介绍： Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports. Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.