Transkingdom network reveals bacterial players associated with cervical cancer gene expression program
| Autor: | Jialu Hu, Richard R. Rodrigues, Khiem C. Lam, Heidi Lyng, Aleksandra E. Sikora, Dariia Vyshenska, Eva Katrine Aarnes, Natalia Shulzhenko, Anja Nilsen, Andrey Morgun, Ryszard A. Zielke, Nicholas Samuel Brown |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
ved/biology.organism_classification_rank.species lcsh:Medicine LAMP3 Prevotellaceae Cervical Cancer Prevotella bivia Microbiology 2.2 Factors relating to physical environment Medical and Health Sciences General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Immune system Clinical Research medicine Genetics 2.2 Factors relating to the physical environment 2.1 Biological and endogenous factors Microbiome Aetiology Gene Cancer Cervical cancer biology ved/biology General Neuroscience Human Genome lcsh:R Computational Biology General Medicine Biological Sciences medicine.disease biology.organism_classification 3. Good health 030104 developmental biology Infectious Diseases Oncology 030220 oncology & carcinogenesis Transkingdom network TAP1 General Agricultural and Biological Sciences Infection |
| Zdroj: | PeerJ, Vol 6, p e5590 (2018) PeerJ, vol 6, iss 9 PeerJ |
| ISSN: | 2167-8359 |
| Popis: | Cervical cancer is the fourth most common cancer in women worldwide with human papillomavirus (HPV) being the main cause the disease. Chromosomal amplifications have been identified as a source of upregulation for cervical cancer driver genes but cannot fully explain increased expression of immune genes in invasive carcinoma. Insight into additional factors that may tip the balance from immune tolerance of HPV to the elimination of the virus may lead to better diagnosis markers. We investigated whether microbiota affect molecular pathways in cervical carcinogenesis by performing microbiome analysis via sequencing 16S rRNA in tumor biopsies from 121 patients. While we detected a large number of intra-tumor taxa (289 operational taxonomic units (OTUs)), we focused on the 38 most abundantly represented microbes. To search for microbes and host genes potentially involved in the interaction, we reconstructed a transkingdom network by integrating a previously discovered cervical cancer gene expression network with our bacterial co-abundance network and employed bipartite betweenness centrality. The top ranked microbes were represented by the familiesBacillaceae,Halobacteriaceae, andPrevotellaceae. While we could not define the first two families to the species level,Prevotellaceaewas assigned toPrevotella bivia. By co-culturing a cervical cancer cell line withP. bivia, we confirmed that three out of the ten top predicted genes in the transkingdom network (lysosomal associated membrane protein 3 (LAMP3), STAT1, TAP1), all regulators of immunological pathways, were upregulated by this microorganism. Therefore, we propose that intra-tumor microbiota may contribute to cervical carcinogenesis through the induction of immune response drivers, including the well-known cancer gene LAMP3. |
| Databáze: | OpenAIRE |
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