Differential expression of MUC1 gene mediated by <italic style="font-style: italic">Fusobacterium nucleatum</italic> in colorectal cancer cells

Xinli YE; Jing LI; Bin TANG; Yuanzhi LAN; Huaxing LUO; Xiaoxue LU; Yuanyuan XIANG; Yan ZHANG; Dongzhu ZENG

doi:10.16016/j.1000-5404.202101166

您当前的位置：

首页 >

文章列表页 >

Differential expression of MUC1 gene mediated by Fusobacterium nucleatum in colorectal cancer cells

Basic Medicine | 更新时间：2026-01-09

- Differential expression of MUC1 gene mediated by Fusobacterium nucleatum in colorectal cancer cells
- Journal of Third Military Medical University Vol. 43, Issue 15, Pages: 1501-1507(2021)
- 作者机构：
  
  1.401120 重庆，重庆医科大学附属第三医院普外科
  2.400038 重庆，陆军军医大学(第三军医大学)药学与检验医学系临床微生物与免疫学教研室
- 作者简介：
- 基金信息：
  
  the Science and Technology Project of Yubei District of Chongqing(2020-35)
- DOI：10.16016/j.1000-5404.202101166
  CLC： R378.2;R394.3;R735.35
- Received：20 January 2021，
  
  Revised：2021-03-30，
  
  Published：15 August 2021
- 稿件说明：
移动端阅览
Xinli YE, Jing LI, Bin TANG, et al. Differential expression of MUC1 gene mediated by Fusobacterium nucleatum in colorectal cancer cells[J]. Journal of Third Military Medical University, 2021, 43(15): 1501-1507.
DOI：

Xinli YE, Jing LI, Bin TANG, et al. Differential expression of MUC1 gene mediated by Fusobacterium nucleatum in colorectal cancer cells[J]. Journal of Third Military Medical University, 2021, 43(15): 1501-1507. DOI： 10.16016/j.1000-5404.202101166.

摘要

目的

通过生物信息学分析具核梭杆菌(

Fusobacterium nucleatum，F.nucleatum，Fn.

)对结直肠癌(colorectal cancer

CRC)差异表达基因(differential expression genes

DEGs)的调控作用，鉴定关键基因在

F.nucleatum

感染结直肠癌细胞中的表达。

方法

利用GEO数据库高通量筛选

F.nucleatum

诱导的结直肠癌差异表达基因；基因本体论(GO)，京都基因和基因组百科全书(KEGG)富集分析差异表达基因数据集；Cytoscape软件构建差异表达基因的蛋白质-蛋白质相互作用网络(PPI)；RT-qPCR和Western blot验证关键(Hub)基因MUC1在细胞模型中的转录水平和蛋白水平表达。

结果

共筛选出118个DEGs，其中20个表达上调，98个下调；GO分析显示DEGs在质膜和质膜的组成部分等细胞成分中富集最显著，KEGG分析发现其在PI3K-Akt、MAPK、Rap1和JAK-STAT等信号通路中有明显富集(

0.05)。在PPI网络中，Hub基因MUC1具有较高的中心性得分，

F.nucleatum

感染与MUC1的差异表达显著相关。

结论

通过对关键基因的筛选和验证，

F.nucleatum

感染致CRC的机制可能与MUC1的过表达有关。

Abstract

Objective

To investigate the regulatory effect of

Fusobacterium nucleatum

(

F.nucleatum

) on differential expression genes (DEGs) in colorectal cancer (CRC) by bioinformatics analysis

and to identify the expression of key genes in

F.nucleatum

infected CRC cells.

Methods

The high-throughput sequencing data of DEGs in CRC regulated by

F.nucleatum

were downloaded and screened from Gene Expression Omnibus (GEO) database

then Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the datasets. Protein-protein interaction (PPI) network of DEGs were subsequently constructed with Cytoscape software. Finally

Western blotting and RT-qPCR were employed to verity the expression of hub gene MUC1 at protein and mRNA levels in the cell model

respectively.

Results

A total of 118 DEGs were screened out

of which 20 were up-regulated and 98 down-regulated. GO analysis showed that DEGs were noticeably enriched in cellular component (CC) such as plasma membrane and integral component of membrane

and KEGG analysis found that DEGs were significantly enriched in PI3K-Akt

MAPK

Rap1 and JAK-STAT signaling pathways (

0.05). In the PPI network

the hub gene MUC1 presented a high centrality score. Western blotting and RT-qPCR indicated that the infection of

F.nucleatum

was significantly correlated with the differential expression of MUC1.

Conclusion

The mechanism of CRC induced by

F.nucleatum

infection may be related to the overexpression of MUC1

according to the screening and verification of hub genes.

关键词

Keywords

references

BRAY F, FERLAY J, SOERJOMATARAM I, et al . Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J ] . CA Cancer J Clin, 2018, 68(6): 394-424. DOI: 10.3322/caac.21492.

CASTELLARIN M, WARREN R L, FREEMAN J D, et al . Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma[J ] . Genome Res, 2012, 22(2): 299-306. DOI: 10.1101/gr.126516.111.

BRENNAN C A, GARRETT W S. Fusobacterium nucleatum-symbiont, opportunist and oncobacterium[J]. Nat Rev Microbiol, 2019, 17(3): 156-166. DOI: 10.1038/s41579-018-0129-6.

NATH S, MUKHERJEE P. MUC1: a multifacetedonco-protein with a key role in cancer progression[J]. Trends Mol Med, 2014, 20(6): 332-342. DOI: 10.1016/j.molmed.2014.02.007.

LAN M S, BATRA S K, QI W N, et al . Cloning and sequencing of a human pancreatic tumor mucincDNA[J ] . J Biol Chem, 1990, 265(25): 15294-15299.

ALAM M, AHMAD R, RAJABI H, et al . MUC1-Concoprotein activates ERK→C/EBPβ signaling and induction of aldehyde dehydrogenase 1A1 in breast cancer cells[J ] . J Biol Chem, 2013, 288(43): 30892-30903. DOI: 10.1074/jbc.m113.477158.

HIRAKI M, SUZUKI Y, ALAM M, et al . MUC1-C stabilizes MCL-1 in the oxidative stress response of triple-negative breast cancer cells to BCL-2inhibitors[J ] . Sci Rep, 2016, 6: 26643. DOI: 10.1038/srep26643.

RAJABI H, ALAM M, TAKAHASHI H, et al . MUC1-Conco-protein activates the ZEB1/miR-200c regulatory loop and epithelial-mesenchymal transition[J ] . Oncogene, 2014, 33(13): 1680-1689. DOI: 10.1038/onc.2013.114.

SZKLARCZYK D, FRANCESCHINI A, WYDER S, et al . STRING v10: protein-protein interaction networks, integrated over the tree of life[J ] . Nucleic Acids Res, 2015, 43(databas e issue): D447-D452. DOI: 10.1093/nar/gku1003.

MENDES R T, NGUYEN D, STEPHENS D, et al . Endothelial cell response to Fusobacterium nucleatum[J ] . Infect Immun, 2016, 84(7): 2141-2148.

HAUSEN H Z. The search for infectious causes of human cancers: where and why[J]. Virology, 2009, 392(1): 1-10. DOI: 10.1016/j.virol.2009.06.001.

TJALSMA H, BOLEIJ A, MARCHESI J R, et al . A bacterial driver-passenger model for colorectal cancer: beyond the usual suspects[J ] . Nat Rev Microbiol, 2012, 10(8) : 575-582. DOI: 10.1038/nrmicro2819.

BAHRAMI A, KHAZAEI M, HASANZADEH M, et al . Therapeutic potential of targeting PI3K/AKT pathway in treatment of colorectal cancer: rational and progress[J ] . J Cell Biochem, 2018, 119(3): 2460-2469. DOI: 10.1002/jcb.25950.

UDDIN S, BAVI P P, HUSSAIN A R, et al . Leptin receptor expression in Middle Eastern colorectal cancer and its potential clinical implication[J ] . Carcinogenesis, 2009, 30(11): 1832-1840. DOI: 10.1093/carcin/bgp145.

UDDIN S, HUSSAIN A R, KHAN O S, et al . Role of dysregulated expression of leptin and leptin receptors in colorectal carcinogenesis[J ] . Tumor Biol, 2014, 35(2): 871-879. DOI: 10.1007/s13277-013-1166-4.

TANG Y, ZHAO Y, SONG X, et al . Tumor-derivedexosomal miRNA-320d as a biomarker for metastatic colorectal cancer[J ] . J Clin Lab Anal, 2019, 33(9): e23004. DOI: 10.1002/jcla.23004.

高志强, 丁志强, 陈勇军, 等. 胰腺癌组织黏蛋白MUC1表达的意义[J]. 世界华人消化杂志, 2006, 14(9): 923-926.

GAO Z Q, DING Z Q, CHEN Y J, et al . Significance of mucin 1 expression in pancreatic cancer tissues[J ] . World Chin J Dig, 2006, 14(9): 923-926.

SHENG Y H, TRIYANA S, WANG R, et al . MUC1 and MUC13 differentially regulate epithelial inflammation in response to inflammatory and infectious stimuli[J ] . Mucosal Immunol, 2013, 6(3): 557-568. DOI: 10.1038/mi.2012.98.

TIAN S, HU J, TAO K, et al . Secreted AGR2 promotes invasion of colorectal cancer cells via Wnt11-mediated non-canonical Wnt signaling[J ] . Exp Cell Res, 2018, 364(2): 198-207. DOI: 10.1016/j.yexcr.2018.02.004..

ZHANG J, HU S, LI Y. KRT18 is correlated with the malignant status and acts as an oncogene in colorectal cancer[J]. Biosci Rep, 2019, 39(8): BSR20190884. DOI: 10.1042/BSR20190884.

HUANG C, LUO H. miR-19-5p enhances tumorigenesis in human colorectal cancer cells by targeting TSPYL5[J]. DNA and Cell Biology, 2018, 37(1): 23-30. DOI: 10.1089/dna.2017.3804.

JU H Q, LU Y X, CHEN D L, et al . Redox regulation of stem-like cells though the CD44v-xCT axis in colorectal cancer: mechanisms and therapeutic implications[J ] . Theranostics, 2016, 6(8): 1160-1175. DOI: 10.7150/thno.14848.

Slattery M L, Lundgreen A, Hines L, et al , Energy homeostasis genes and breast cancer risk: The influence of ancestry, body size, and menopausal status, the breast cancer health disparities study[J ] . Cancer Epidemiol, 2015, 39(6) : 1113-1122. DOI: 10.1016/j.canep.2015.08.012.

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

MiR-543/SNTB1 axis modulates immune microenvironment in colorectal cancer

Efficacy and safety of immunotherapy combined with targeted therapy and chemotherapy in third-line treatment of microsatellite stable metastatic colorectal cancer

Preparation of nanosized hypoxia-inducible factor 1α inhibitor and its application in reversing chemoresistance in colorectal cancer cells

Plateau hypoxia improves tumor immune microenvironment and inhibits subcutaneous tumor growth of colorectal cancer

Value of energy spectrum CT volume quantitative parameters in differentiating pathological types of colorectal cancer

Related Author

ZHANG Min

LI Min

XIAO Meng

CHEN Cai

ZHENG Xiaoju

LEI Yuguang

ZHAO Wensi

SONG Jian

Related Institution

School of Medicine, Xinyang Hospital of Traditional Chinese Medicine

School of Pharmaceutical Sciences， Xinyang Vocational and Technical College， Xinyang， Henan, Xinyang Hospital of Traditional Chinese Medicine

Department of Pathology, Xinyang Hospital of Traditional Chinese Medicine

Department of Oncology, Renmin Hospital of Wuhan University

Department of Pharmacy, Renmin Hospital of Wuhan University

⁰

Differential expression of MUC1 gene mediated by Fusobacterium nucleatum in colorectal cancer cells

DOI：10.16016/j.1000-5404.202101166

摘要

Abstract

关键词

Keywords

references