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微生物群组成及其对结直肠癌DNA甲基化的影响。

Microbiota composition and its impact on DNA methylation in colorectal cancer.

作者信息

Gutierrez-Angulo Melva, Ayala-Madrigal Maria de la Luz, Moreno-Ortiz Jose Miguel, Peregrina-Sandoval Jorge, Garcia-Ayala Fernando Daniel

机构信息

Departamento de Ciencias de la Salud, Centro Universitario de los Altos, Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.

Doctorado en Genética Humana e Instituto de Genética Humana "Dr. Enrique Corona Rivera", Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud (CUCS), Universidad de Guadalajara, Guadalajara, Jalisco, Mexico.

出版信息

Front Genet. 2023 Aug 8;14:1037406. doi: 10.3389/fgene.2023.1037406. eCollection 2023.

Abstract

Colorectal cancer is a complex disease resulting from the interaction of genetics, epigenetics, and environmental factors. DNA methylation is frequently found in tumor suppressor genes to promote cancer development. Several factors are associated with changes in the DNA methylation pattern, and recently, the gastrointestinal microbiota could be associated with this epigenetic change. The predominant phyla in gut microbiota are Firmicutes and Bacteroidetes; however, an enrichment of , , and , among others, has been reported in colorectal cancer, although the composition could be influenced by several factors, including diet, age, sex, and cancer stage, a gram-negative anaerobic bacillus, is mainly associated with colorectal cancer patients positive for the CpG island methylator phenotype, although hypermethylation in genes such as , , , , , , and has also been described. Moreover, , a gram-positive, rod-shaped bacterium, is related to hypermethylation in , , , , , , , and genes. The underlying epigenetic mechanism is unclear, although it could be implicated in the regulation of DNA methyltransferases, enzymes that catalyze the transfer of a methyl group on cytosine of CpG sites. Since DNA methylation is a reversible event, changes in gut microbiota could modulate the gene expression through DNA methylation and improve the colorectal cancer prognosis.

摘要

结直肠癌是一种由遗传、表观遗传和环境因素相互作用导致的复杂疾病。DNA甲基化在肿瘤抑制基因中频繁出现,以促进癌症发展。有几个因素与DNA甲基化模式的变化有关,最近,胃肠道微生物群可能与这种表观遗传变化有关。肠道微生物群中的主要门类是厚壁菌门和拟杆菌门;然而,尽管其组成可能受饮食、年龄、性别和癌症分期等多种因素影响,但在结直肠癌中已报道了诸如……等的富集。具核梭杆菌是一种革兰氏阴性厌氧杆菌,主要与CpG岛甲基化表型阳性的结直肠癌患者相关,尽管也已描述了如……等基因的高甲基化。此外,迟缓埃格特菌是一种革兰氏阳性杆状细菌,与……等基因的高甲基化有关。潜在的表观遗传机制尚不清楚,尽管它可能与DNA甲基转移酶的调节有关,DNA甲基转移酶是催化CpG位点胞嘧啶上甲基基团转移的酶。由于DNA甲基化是一个可逆事件,肠道微生物群的变化可能通过DNA甲基化调节基因表达并改善结直肠癌的预后。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23fe/10442805/12bdfb6b983c/fgene-14-1037406-g001.jpg

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