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Parvimonas micra activates the Ras/ERK/c-Fos pathway by upregulating miR-218-5p to promote colorectal cancer progression

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in the world, and a strong relationship exists between CRC and gut microbiota, which affects the occurrence, development, and metastasis of cancer. Bioinformatics-based analyses revealed that the abundance of Parvimonas micra (P. mi...

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Autores principales: Chang, Yuxiao, Huang, Ziran, Hou, Fengyi, Liu, Yuejiao, Wang, Likun, Wang, Zhen, Sun, Yifan, Pan, Zhiyuan, Tan, Yafang, Ding, Lei, Gao, Hong, Yang, Ruifu, Bi, Yujing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9830783/
https://www.ncbi.nlm.nih.gov/pubmed/36627634
http://dx.doi.org/10.1186/s13046-022-02572-2
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author Chang, Yuxiao
Huang, Ziran
Hou, Fengyi
Liu, Yuejiao
Wang, Likun
Wang, Zhen
Sun, Yifan
Pan, Zhiyuan
Tan, Yafang
Ding, Lei
Gao, Hong
Yang, Ruifu
Bi, Yujing
author_facet Chang, Yuxiao
Huang, Ziran
Hou, Fengyi
Liu, Yuejiao
Wang, Likun
Wang, Zhen
Sun, Yifan
Pan, Zhiyuan
Tan, Yafang
Ding, Lei
Gao, Hong
Yang, Ruifu
Bi, Yujing
author_sort Chang, Yuxiao
collection PubMed
description BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in the world, and a strong relationship exists between CRC and gut microbiota, which affects the occurrence, development, and metastasis of cancer. Bioinformatics-based analyses revealed that the abundance of Parvimonas micra (P. micra) in the feces of patients with cancer is significantly higher than that in healthy people. Therefore, an important relationship may exist between P. micra and CRC. METHODS: We first confirmed that P. micra can promote the proliferation of cell lines through cell experiments and mouse models. Then we selected the signaling pathways and content of exosomes to promote the development of CRC by transcriptomics and microRNA sequencing. Finally, we confirmed that P. micra promoted CRC development through miR-218-5p/Ras/ERK/c-Fos pathway through the in vivo and in vitro experiments. RESULTS: First, it was confirmed by in vitro and in vivo experiments that P. micra can promote the development of CRC. Transcriptome analysis after the coincubation of bacteria and cells revealed that P. micra promoted cell proliferation by activating the Ras/ERK/c-Fos pathway. Furthermore, microRNA sequencing analysis of the cells and exosomes showed that miR-218-5p and protein tyrosine phosphatase receptor R (PTPRR) were the key factors involved in activating the Ras/ERK/c-Fos pathway, and the miR-218-5p inhibitor was used to confirm the role of microRNA in xenograft mice. CONCLUSION: This experiment confirmed that P. micra promoted the development of CRC by upregulating miR-218-5p expression in cells and exosomes, inhibiting PTPRR expression, and ultimately activating the Ras/ERK/c-Fos signaling pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-022-02572-2.
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spelling pubmed-98307832023-01-11 Parvimonas micra activates the Ras/ERK/c-Fos pathway by upregulating miR-218-5p to promote colorectal cancer progression Chang, Yuxiao Huang, Ziran Hou, Fengyi Liu, Yuejiao Wang, Likun Wang, Zhen Sun, Yifan Pan, Zhiyuan Tan, Yafang Ding, Lei Gao, Hong Yang, Ruifu Bi, Yujing J Exp Clin Cancer Res Research BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in the world, and a strong relationship exists between CRC and gut microbiota, which affects the occurrence, development, and metastasis of cancer. Bioinformatics-based analyses revealed that the abundance of Parvimonas micra (P. micra) in the feces of patients with cancer is significantly higher than that in healthy people. Therefore, an important relationship may exist between P. micra and CRC. METHODS: We first confirmed that P. micra can promote the proliferation of cell lines through cell experiments and mouse models. Then we selected the signaling pathways and content of exosomes to promote the development of CRC by transcriptomics and microRNA sequencing. Finally, we confirmed that P. micra promoted CRC development through miR-218-5p/Ras/ERK/c-Fos pathway through the in vivo and in vitro experiments. RESULTS: First, it was confirmed by in vitro and in vivo experiments that P. micra can promote the development of CRC. Transcriptome analysis after the coincubation of bacteria and cells revealed that P. micra promoted cell proliferation by activating the Ras/ERK/c-Fos pathway. Furthermore, microRNA sequencing analysis of the cells and exosomes showed that miR-218-5p and protein tyrosine phosphatase receptor R (PTPRR) were the key factors involved in activating the Ras/ERK/c-Fos pathway, and the miR-218-5p inhibitor was used to confirm the role of microRNA in xenograft mice. CONCLUSION: This experiment confirmed that P. micra promoted the development of CRC by upregulating miR-218-5p expression in cells and exosomes, inhibiting PTPRR expression, and ultimately activating the Ras/ERK/c-Fos signaling pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13046-022-02572-2. BioMed Central 2023-01-10 /pmc/articles/PMC9830783/ /pubmed/36627634 http://dx.doi.org/10.1186/s13046-022-02572-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Chang, Yuxiao
Huang, Ziran
Hou, Fengyi
Liu, Yuejiao
Wang, Likun
Wang, Zhen
Sun, Yifan
Pan, Zhiyuan
Tan, Yafang
Ding, Lei
Gao, Hong
Yang, Ruifu
Bi, Yujing
Parvimonas micra activates the Ras/ERK/c-Fos pathway by upregulating miR-218-5p to promote colorectal cancer progression
title Parvimonas micra activates the Ras/ERK/c-Fos pathway by upregulating miR-218-5p to promote colorectal cancer progression
title_full Parvimonas micra activates the Ras/ERK/c-Fos pathway by upregulating miR-218-5p to promote colorectal cancer progression
title_fullStr Parvimonas micra activates the Ras/ERK/c-Fos pathway by upregulating miR-218-5p to promote colorectal cancer progression
title_full_unstemmed Parvimonas micra activates the Ras/ERK/c-Fos pathway by upregulating miR-218-5p to promote colorectal cancer progression
title_short Parvimonas micra activates the Ras/ERK/c-Fos pathway by upregulating miR-218-5p to promote colorectal cancer progression
title_sort parvimonas micra activates the ras/erk/c-fos pathway by upregulating mir-218-5p to promote colorectal cancer progression
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9830783/
https://www.ncbi.nlm.nih.gov/pubmed/36627634
http://dx.doi.org/10.1186/s13046-022-02572-2
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