Mitochondria govern histone acetylation in colorectal cancer
Mitochondria govern histone acetylation in colorectal cancer
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DOI：
10.1002/path.5818
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发表时间：
2021-10
期刊：
影响因子：
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通讯作者：
K. Ohshima;R. Oi;S. Nojima;E. Morii
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文献类型：
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作者：
K. Ohshima;R. Oi;S. Nojima;E. Morii
癌细胞具有支持其生长的改变的代谢状态，例如有氧糖酵解，称为瓦尔堡效应。据报道，结肠直肠癌细胞表现出瓦尔堡效应，并且主要依赖于糖酵解进行进展，并且具有功能失调的线粒体。到目前为止，线粒体功能如何影响结直肠癌细胞的特性尚不清楚。在这里，我们证明了线粒体在结直肠癌细胞中维持组蛋白乙酰化，特别是乙酰化组蛋白H3赖氨酸27（H3K27ac），这是活性超级增强子的替代表观基因组标志物。对人结直肠腺癌标本进行免疫组织化学染色，结果显示，与邻近非肿瘤性粘膜相比，腺癌病变中的线粒体质量和H3K27ac标记增加。使用线粒体呼吸复合物抑制剂或线粒体DNA缺失的人结直肠癌细胞后的免疫印迹显示，线粒体保持了泛组蛋白乙酰化和H3K27ac标记。值得注意的是，锚定非依赖性生长（癌症的一个特征）增加了人结直肠癌细胞中的线粒体质量和H3K27ac标记。这些发现表明，人类结直肠癌细胞中的线粒体并不像以前认为的那样功能失调，而是作为组蛋白乙酰化的诱导剂发挥作用。© 2021大不列颠和爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
Cancer cells have an altered metabolic state that supports their growth, for example, aerobic glycolysis, known as the Warburg effect. Colorectal cancer cells have been reported to exhibit the Warburg effect and mainly rely on glycolysis for progression and have dysfunctional mitochondria. So far, how mitochondrial function influences the properties of colorectal cancer cells is unclear. Here, we demonstrated that mitochondria maintain histone acetylation, in particular acetylated histone H3 lysine 27 (H3K27ac), a surrogate epigenomic marker of active super‐enhancers, in colorectal cancer cells. Immunohistochemistry was used on human colorectal adenocarcinoma specimens and showed that mitochondrial mass and H3K27ac marks were increased in adenocarcinoma lesions compared with adjacent non‐neoplastic mucosa. Immunoblotting after using inhibitors of the mitochondrial respiratory complex or mitochondrial DNA‐depleted human colorectal cancer cells revealed that mitochondria maintained pan‐histone acetylation and H3K27ac marks. Notably, anchorage‐independent growth, a feature of cancer, increased mitochondrial mass and H3K27ac marks in human colorectal cancer cells. These findings indicate that mitochondria in human colorectal cancer cells are not dysfunctional, as formerly believed, but function as inducers of histone acetylation. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.