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Gut microbiota regulate tumor metastasis via circRNA/miRNA networks


research target:Gut microbiota; cancer; cancer stem cell; circular RNA (circRNA); interleukin-11(IL-11); metastasis; microRNA
Periodicals:Gut Microbes
IF:10.244
Cooperative Unit:Tongji University School of Medicine
Time of publication:November,2020
 




Summary


Background: Increasing evidence indicates that gut microbiota plays an important role in cancer progression. However, the underlying mechanism remains largely unknown. Here, we report that broad-spectrum antibiotics (ABX) treatment leads to enhanced metastasis by the alteration of gut microbiome composition.
 
Methods: Cancer LLC and B16-F10 cell metastasis mouse models, and microarray/RNA sequencing analysis were used to reveal the regulatory functions of microbiota-mediated circular RNA (circRNA)/microRNA (miRNA) networks that may contribute to cancer metastasis.
 
Results: The specific pathogen-free (SPF) mice with ABX treatment demonstrated enhanced lung metastasis. Fecal microbiota transplantation (FMT) from SPF mice or Bifidobacterium into germ-free mice significantly suppressed lung metastasis. Mechanistically, gut microbiota impacts circRNA expression to regulate levels of corresponding miRNAs. Specifically, such modulations of gut microbiota inhibit mmu_circ_0000730 expression in an IL-11-dependent manner. Bioinformatics analysis combined with luciferase reporter assays revealed reciprocal repression between mmu_circ_0000730 and mmu-miR-466i-3p. We further showed that both mmu-miR-466i-3p and mmu-miR-466 f-3p suppresses a number of genes involved in epithelial-mesenchymal transition (EMT) and stemness of cancer stem cells such as SOX9.
 
Conclusions: These results provide evidence of a previously unrecognized regulatory role of non-coding RNAs in microbiota-mediated cancer metastasis, and thus, the microbiome may serve as a therapeutic target.
 
Keywords: Gut microbiota; cancer; cancer stem cell; circular RNA (circRNA); interleukin-11(IL-11); metastasis; microRNA




Partial results of cooperation







BersinbioTM cooperative technology:RNA pull-down
Original link:
10.1080/19490976.2020.1788891