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Review
. 2023 Jun 23;24(13):10520.
doi: 10.3390/ijms241310520.

Cross-Kingdom Interaction of miRNAs and Gut Microbiota with Non-Invasive Diagnostic and Therapeutic Implications in Colorectal Cancer

Ondrej Pös  1   2 , Jakub Styk  1   2   3 , Gergely Buglyó  4 , Michal Zeman  1 , Lydia Lukyova  5 , Kamila Bernatova  5 , Evelina Hrckova Turnova  1   6 , Tomas Rendek  3 , Ádám Csók  4 , Vanda Repiska  3   7 , Bálint Nagy  1   4 , Tomas Szemes  1   2   5
Affiliations
Review

Cross-Kingdom Interaction of miRNAs and Gut Microbiota with Non-Invasive Diagnostic and Therapeutic Implications in Colorectal Cancer

Ondrej Pös et al. Int J Mol Sci. .

Abstract

Colorectal cancer (CRC) has one of the highest incidences among all types of malignant diseases, affecting millions of people worldwide. It shows slow progression, making it preventable. However, this is not the case due to shortcomings in its diagnostic and management procedure and a lack of effective non-invasive biomarkers for screening. Here, we discuss CRC-associated microRNAs (miRNAs) and gut microbial species with potential as CRC diagnostic and therapy biomarkers. We provide rich evidence of cross-kingdom miRNA-mediated interactions between the host and gut microbiome. miRNAs have emerged with the ability to shape the composition and dynamics of gut microbiota. Intestinal microbes can uptake miRNAs, which in turn influence microbial growth and provide the ability to regulate the abundance of various microbial species. In the context of CRC, targeting miRNAs could aid in manipulating the balance of the microbiota. Our findings suggest the need for correlation analysis between the composition of the gut microbiome and the miRNA expression profile.

Keywords: biomarkers; colorectal cancer; dysbiosis; gut microbiota; microRNAs.

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Conflict of interest statement

The authors G.B., M.Z., L.L., K.B., E.H.T., T.R., A.C., V.R., and B.N. declare no conflicts of interest that could influence the work reported in this paper. O.P., J.S., and T.S. are employees of Geneton Ltd. and are involved in numerous research and development efforts for adapting new technologies to better understand genomic data and facilitate their implementation in patient care.

Figures

Figure 3
Figure 3
A scheme of F. nucleatum-mediated CRC development via miRNA interactions. However, not all the proposed miRNA interactions have yet been confirmed by functional studies [27,108,109,112,113,114,115]. Explanatory notes: red arrows (↓) represent decreased level; green arrows (↑) represent increased level; black arrows describe direct stimulatory modification or transcriptional activation of gene expression; red bunt-ended lines (T) describe direct inhibitory effect (created with BioRender.com).
Figure 1
Figure 1
PubMed publication records searching for the terms (miRNA) AND (body fluids) suggest emerging research interest in cell-free miRNAs since 2009 [18,19].
Figure 2
Figure 2
Known types of miRNA-mediated interactions between host and gut microbiota. Human-host–microbiome communication is affected by endogenous and exogenous factors. Both host and microorganisms produce miRNAs to regulate gene expression, while miRNA self-regulation has also been described. However, host-derived miRNAs have shown the ability to regulate microbiome gene expression, and microbial miRNAs and miRNA-like molecules can regulate gene expression of the host. Although self-regulation of microbial miRNAs, as well as interactions between host miRNAs and microbial miRNA molecules, can be hypothesized, these mechanisms have yet to be confirmed. Moreover, several cross-kingdom miRNA interactions have been described, but such communication in the gut microbiome is understudied (created with BioRender.com).
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