MicroRNA Modulation in Cancer Progression and Therapeutics

MicroRNAs (miRNAs) are short non-coding RNAs that fine-tune gene expression by directing sequence-specific repression of messenger RNAs. In cancer, aberrant miRNA expression underlies hallmarks of tumourigenesis, including uncontrolled proliferation, evasion of apoptosis, metabolic reprogramming and metastatic dissemination. Oncogenic miRNAs (oncomiRs) often target tumour suppressors, whereas tumour-suppressive miRNAs silence drivers of malignancy. Restoring the balance of these networks has emerged as a promising therapeutic strategy. Approaches include synthetic miRNA mimics to replenish lost suppressors, antimiR oligonucleotides to inhibit oncomiRs and advanced delivery vehicles to overcome stability and targeting challenges. Clinical interest has grown in miRNAs as diagnostic and prognostic biomarkers, given their stability in bodily fluids and correlation with tumour stage, therapeutic response and patient survival. Integration of high-throughput profiling, functional screens and delivery science is accelerating translation. The global significance of miRNA modulation extends beyond single tumour types, offering a unifying platform for precision oncology interventions and combinatorial regimens with conventional chemotherapy or targeted agents.

Research from Nature Portfolio

Recent studies have demonstrated that depletion of specific miRNAs can drive malignant progression through metabolic rewiring. In a chronic myeloid leukaemia model, loss of a single suppressive miRNA in stem cells led to blast crisis by enhancing fatty acid β-oxidation, oxidative phosphorylation and mitochondrial fusion. Restoration of this miRNA via a synthetic CpG-linked mimic oligodeoxynucleotide reversed the aggressive phenotype in both genetically engineered mice and patient-derived xenografts, illustrating the therapeutic potential of targeted miRNA replacement in leukaemic stem cells.

MicroRNA Modulation in Cancer Progression and Therapeutics publication trend

The graph below shows the total number of articles in microrna modulation in cancer progression and therapeutics across all publications each year (not limited to Nature Index journals).

Technical terms

microRNA (miRNA): Short non-coding RNA molecules that regulate gene expression post-transcriptionally by base pairing with target mRNAs.

OncomiR: A microRNA with oncogenic activity, typically downregulating tumour suppressor genes.

Mimic oligodeoxynucleotide: A synthetic nucleic acid designed to restore the function of a specific miRNA.

Epitheli●al–mesenchymal transition (EMT): A process by which epithelial cells acquire mesenchymal traits, increasing motility and invasiveness.

Xenograft: A tumour model in which human cancer cells are transplanted into immunodeficient mice to study therapy responses.

Elastin-like polypeptide nanoparticle: A recombinant carrier that undergoes phase transition to protect and deliver miRNA cargo to tumour cells.

References

1. Acquired miR-142 deficit in leukemic stem cells suffices to drive chronic myeloid leukemia into blast crisis. Nature Communications (2023).
2. CMC: Cancer miRNA Census – a list of cancer-related miRNA genes. Nucleic Acids Research (2024).
3. CRISPR/Cas9-mediated inactivation of miR-34a and miR-34b/c in HCT116 colorectal cancer cells: comprehensive characterization after exposure to 5-FU reveals EMT and autophagy as key processes regulated by miR-34. Cell Death & Differentiation (2023).
4. Multifunctional elastin-like polypeptide nanocarriers for efficient miRNA delivery in cancer therapy. Journal of Nanobiotechnology (2024).