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CRC 患者共生大肠杆菌的 OmpA 影响 HCT116 结肠癌细胞系的细胞凋亡。

The OmpA of commensal Escherichia coli of CRC patients affects apoptosis of the HCT116 colon cancer cell line.

机构信息

Student Research Committee, Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Department of Pathology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

BMC Microbiol. 2022 May 19;22(1):139. doi: 10.1186/s12866-022-02540-y.

DOI:10.1186/s12866-022-02540-y
PMID:35590263
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9118694/
Abstract

BACKGROUND

Colorectal cancer ranks third globally among all types of cancers. Dysbiosis of the gut microbiota of people with CRC is one of the effective agents in the tumorigenesis and metastasis in this type of cancer. The population of Escherichia coli strains, a component of gut microbiota, is increased in the gut of people with CRC compared with healthy people. So, E.coli strains isolated from these patients may have a role in tumorigenesis. Because the most isolated strains belong to the B2 phylogenuetic group, there seems to be a linkage between the bacterium components and malignancy.

MATERIAL AND METHODS

In this study, the proteomic comparison between isolated Ecoli from CRC patients and healthy people was assayed. The isolated spot was studied by Two-dimensional gel electrophoresis (2DE) and Liquid chromatography-mass spectrometry (LC-MS). The results showed that the expression of Outer membrane protein A (OmpA) protein increased in the commensal E.coli B2 phylogenetic group isolated from CRC patients. Additionally, we analyzed the effect of the OmpA protein on the expression of the four genes related to apoptosis in the HCT116 colon cancer cell line.

RESULTS

This study identified that OmpA protein was overexpressed in the commensal E.coli B2 phylogenetic group isolated from CRC patients compared to the E.coli from the control group. This protein significantly decreased the expression of Bax and Bak, pro-apoptotic genes, as well as the expression of P53 in the HCT116 Cell Line, P < 0.0001. LC-MS and protein bioinformatics results confirmed that this protein is outer membrane protein A, which can bind to nucleic acid and some of the organelle proteins on the eukaryotic cell surface.

CONCLUSIONS

According to our invitro and insilico investigations, OmpA of gut E.coli strains that belong to the B2 phylogenetic group can affect the eukaryotic cell cycle.

摘要

背景

结直肠癌在所有癌症类型中全球排名第三。CRC 患者肠道微生物群落的失调是此类癌症发生和转移的有效因素之一。与健康人相比,CRC 患者肠道中大肠杆菌菌株(肠道微生物群落的组成部分)的数量增加。因此,从这些患者中分离出的大肠杆菌菌株可能在肿瘤发生中起作用。由于最分离的菌株属于 B2 系统发育群,因此细菌成分与恶性肿瘤之间似乎存在联系。

材料和方法

在这项研究中,对从 CRC 患者和健康人分离的大肠杆菌进行了蛋白质组比较。通过二维凝胶电泳(2DE)和液相色谱-质谱(LC-MS)研究分离的斑点。结果表明,CRC 患者共生大肠杆菌 B2 系统发育群中外膜蛋白 A(OmpA)蛋白的表达增加。此外,我们分析了 OmpA 蛋白对 HCT116 结肠癌细胞系中与凋亡相关的四个基因表达的影响。

结果

本研究确定与对照组相比,从 CRC 患者中分离的共生大肠杆菌 B2 系统发育群中 OmpA 蛋白表达增加。该蛋白显著降低了 Bax 和 Bak 等促凋亡基因以及 HCT116 细胞系中 P53 的表达,P<0.0001。LC-MS 和蛋白质生物信息学结果证实,该蛋白是外膜蛋白 A,可与真核细胞表面的核酸和一些细胞器蛋白结合。

结论

根据我们的体外和计算机研究,属于 B2 系统发育群的肠道大肠杆菌菌株的 OmpA 可以影响真核细胞周期。

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