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

Journal of Experimental & Clinical Cancer Research

Research

Hong Gao¹  Lei Ding¹  Ziran Huang²  Ruifu Yang²  Yifan Sun²  Zhiyuan Pan²  Zhen Wang²  Yafang Tan²  Yuxiao Chang²  Likun Wang²  Yuejiao Liu²  Yujing Bi²  Fengyi Hou² 

[1] Department of Colorectal Surgery, Department of General Surgery, Beijing Shijitan Hospital, Capital Medical University, 100038, Beijing, China;State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 100071, Beijing, China;

关键词: Parvimonas micra;    CRC;    Exosomes;    microRNA;    Colorectal cancer;    Ras/ERK/c-Fos signaling pathway;   

DOI  :  10.1186/s13046-022-02572-2

 received in 2022-09-03, accepted in 2022-12-14,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundColorectal 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.MethodsWe 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.ResultsFirst, 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.ConclusionThis 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.

【 授权许可】

CC BY   
© The Author(s) 2023

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