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Promotion of Deoxycholic Acid Effect on Colonic Cancer Cell Lines In Vitro by Altering the Mucosal Microbiota

Colorectal cancer (CRC) is the third most prevalent neoplasm and the second leading cause of cancer death worldwide. Microbiota and their products, such as bile acids (BAs), are important causal factors for the occurrence and development of CRC. Therefore, we performed 16S ribosomal RNA (16S rRNA) a...

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Autores principales: Ma, Yanpeng, Zhang, Yi, Qu, Ruize, Zhou, Xin, Sun, Lulu, Wang, Kai, Jiang, Changtao, Zhang, Zhipeng, Fu, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9788287/
https://www.ncbi.nlm.nih.gov/pubmed/36557741
http://dx.doi.org/10.3390/microorganisms10122486
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author Ma, Yanpeng
Zhang, Yi
Qu, Ruize
Zhou, Xin
Sun, Lulu
Wang, Kai
Jiang, Changtao
Zhang, Zhipeng
Fu, Wei
author_facet Ma, Yanpeng
Zhang, Yi
Qu, Ruize
Zhou, Xin
Sun, Lulu
Wang, Kai
Jiang, Changtao
Zhang, Zhipeng
Fu, Wei
author_sort Ma, Yanpeng
collection PubMed
description Colorectal cancer (CRC) is the third most prevalent neoplasm and the second leading cause of cancer death worldwide. Microbiota and their products, such as bile acids (BAs), are important causal factors for the occurrence and development of CRC. Therefore, we performed 16S ribosomal RNA (16S rRNA) and liquid chromatography/mass spectrometry (LC–MS) to measure mucosal microbiota and BA composition in paired cancerous and noncancerous gut tissue samples from 33 patients with CRC at a hospital in Beijing. In cancerous tissues, we detected altered mucosal microbiota with increased levels of the genera Bacteroides, Curtobacterium, and Campylobacter and an increase in deoxycholic acid (DCA), which was the only BA elevated in cancerous tissues. Ex vivo coculture showed that the mucosal microbiota in cancerous tissues indeed had a stronger DCA production ability, indicating that DCA-producing bacteria are enriched in tumors. Results from the CCK8 and Transwell assays indicated that DCA enhances the overgrowth, migration, and invasion of CRC cell lines, and, through qPCR and Western blot analyses, downregulation of FXR was observed in CRC cell lines after DCA culture. We then verified the downregulation of FXR expression in cancerous tissues using our data and the TCGA database, and we found that FXR downregulation plays an important role in the development of CRC. In conclusion, differing mucosal microbiota, increased amounts of mucosal DCA, and lower FXR expression were demonstrated in cancerous tissues compared to normal tissue samples. The results of this study can be applied to the development of potential therapeutic targets for CRC prevention, such as altering mucosal microbiota, DCA, or FXR.
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spelling pubmed-97882872022-12-24 Promotion of Deoxycholic Acid Effect on Colonic Cancer Cell Lines In Vitro by Altering the Mucosal Microbiota Ma, Yanpeng Zhang, Yi Qu, Ruize Zhou, Xin Sun, Lulu Wang, Kai Jiang, Changtao Zhang, Zhipeng Fu, Wei Microorganisms Article Colorectal cancer (CRC) is the third most prevalent neoplasm and the second leading cause of cancer death worldwide. Microbiota and their products, such as bile acids (BAs), are important causal factors for the occurrence and development of CRC. Therefore, we performed 16S ribosomal RNA (16S rRNA) and liquid chromatography/mass spectrometry (LC–MS) to measure mucosal microbiota and BA composition in paired cancerous and noncancerous gut tissue samples from 33 patients with CRC at a hospital in Beijing. In cancerous tissues, we detected altered mucosal microbiota with increased levels of the genera Bacteroides, Curtobacterium, and Campylobacter and an increase in deoxycholic acid (DCA), which was the only BA elevated in cancerous tissues. Ex vivo coculture showed that the mucosal microbiota in cancerous tissues indeed had a stronger DCA production ability, indicating that DCA-producing bacteria are enriched in tumors. Results from the CCK8 and Transwell assays indicated that DCA enhances the overgrowth, migration, and invasion of CRC cell lines, and, through qPCR and Western blot analyses, downregulation of FXR was observed in CRC cell lines after DCA culture. We then verified the downregulation of FXR expression in cancerous tissues using our data and the TCGA database, and we found that FXR downregulation plays an important role in the development of CRC. In conclusion, differing mucosal microbiota, increased amounts of mucosal DCA, and lower FXR expression were demonstrated in cancerous tissues compared to normal tissue samples. The results of this study can be applied to the development of potential therapeutic targets for CRC prevention, such as altering mucosal microbiota, DCA, or FXR. MDPI 2022-12-15 /pmc/articles/PMC9788287/ /pubmed/36557741 http://dx.doi.org/10.3390/microorganisms10122486 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ma, Yanpeng
Zhang, Yi
Qu, Ruize
Zhou, Xin
Sun, Lulu
Wang, Kai
Jiang, Changtao
Zhang, Zhipeng
Fu, Wei
Promotion of Deoxycholic Acid Effect on Colonic Cancer Cell Lines In Vitro by Altering the Mucosal Microbiota
title Promotion of Deoxycholic Acid Effect on Colonic Cancer Cell Lines In Vitro by Altering the Mucosal Microbiota
title_full Promotion of Deoxycholic Acid Effect on Colonic Cancer Cell Lines In Vitro by Altering the Mucosal Microbiota
title_fullStr Promotion of Deoxycholic Acid Effect on Colonic Cancer Cell Lines In Vitro by Altering the Mucosal Microbiota
title_full_unstemmed Promotion of Deoxycholic Acid Effect on Colonic Cancer Cell Lines In Vitro by Altering the Mucosal Microbiota
title_short Promotion of Deoxycholic Acid Effect on Colonic Cancer Cell Lines In Vitro by Altering the Mucosal Microbiota
title_sort promotion of deoxycholic acid effect on colonic cancer cell lines in vitro by altering the mucosal microbiota
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9788287/
https://www.ncbi.nlm.nih.gov/pubmed/36557741
http://dx.doi.org/10.3390/microorganisms10122486
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