MicroRNA Regulation in Epithelial-Mesenchymal Transition and Cancer Metastasis

MicroRNAs (miRNAs) are small non-coding RNAs that orchestrate post-transcriptional gene regulation and have emerged as pivotal modulators of epithelial-mesenchymal transition (EMT), a process by which epithelial cells acquire mesenchymal characteristics to enable invasion, dissemination and colonisation of distant organs. During EMT, epithelial markers such as E-cadherin are downregulated by transcription factors including ZEB1, ZEB2, SNAIL and TWIST, while mesenchymal markers such as vimentin and N-cadherin are induced. Specific miRNAs form double-negative feedback loops with these EMT transcription factors, creating bistable switches that determine cell phenotype and plasticity. The miR-200 family in particular maintains the epithelial state through direct repression of ZEB1 and ZEB2. Conversely, loss of these miRNAs facilitates a mesenchymal programme conducive to intravasation, survival in circulation and colonisation at secondary sites. Beyond EMT regulation, miRNAs modulate key signalling pathways—including TGF-β, Wnt and Notch—and influence the tumour microenvironment, angiogenesis and immune evasion. Circulating miRNAs shed from tumours present as minimally invasive biomarkers for early detection of metastatic disease, while chemically stabilised miRNA mimics and antagomirs offer novel therapeutic avenues. The pleiotropic nature of miRNA regulation underpins both heterogeneity and adaptability of cancer cells, highlighting their global significance in oncology and the promise of miRNA-based diagnostics and treatments.

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MicroRNA Regulation in Epithelial-Mesenchymal Transition and Cancer Metastasis publication trend

The graph below shows the total number of articles in microrna regulation in epithelial-mesenchymal transition and cancer metastasis across all publications each year (not limited to Nature Index journals).

Technical terms

microRNA: A short non-coding RNA molecule (~22 nucleotides) that regulates gene expression by binding target mRNAs to inhibit translation or promote degradation.

Epithelial-Mesenchymal Transition (EMT): A biological program in which epithelial cells lose polarity and adhesion and acquire motile, mesenchymal traits, facilitating invasion and metastasis.

Metastasis: The multistep process by which cancer cells disseminate from a primary tumour to establish secondary tumours in distant organs.

Transcription factor: A protein that binds specific DNA sequences to regulate transcription; key examples in EMT include ZEB1, ZEB2, SNAIL and TWIST.

Circulating biomarker: A molecule detectable in body fluids whose levels reflect disease presence or progression, offering a minimally invasive diagnostic tool.

miRNA mimic: A chemically synthesised oligonucleotide designed to emulate the function of an endogenous miRNA, often modified to enhance stability and target specificity.

References

1. Chemical modification patterns for microRNA therapeutic mimics: a structure-activity relationship (SAR) case-study on miR-200c. Nucleic Acids Research (2024).
2. Unraveling the metastasis‐preventing effect of miR‐200c in vitro and in vivo. Molecular Oncology (2024).
3. The miR-200 Family of microRNAs: Fine Tuners of Epithelial-Mesenchymal Transition and Circulating Cancer Biomarkers. Cancers (2021).
4. The miR-200 Family Inhibits Epithelial-Mesenchymal Transition and Cancer Cell Migration by Direct Targeting of E-cadherin Transcriptional Repressors ZEB1 and ZEB2 *. Journal of Biological Chemistry (2008).
5. MicroRNA Control of TGF-β Signaling. International Journal of Molecular Sciences (2018).
6. The Regulatory Role of MicroRNAs in EMT and Cancer. Journal of Oncology (2015).