MicroRNA-181 Family in Cancer Biology and Therapeutics

The microRNA-181 family comprises a highly conserved group of small noncoding RNAs that orchestrate gene expression at the post-transcriptional level. Members of this family—miR-181a, miR-181b, miR-181c and miR-181d—modulate key hallmarks of cancer, including cell proliferation, apoptosis, epithelial–mesenchymal transition (EMT), angiogenesis and immune evasion. Aberrant expression of miR-181 family members has been documented across a broad spectrum of malignancies, from hepatocellular carcinoma to glioblastoma and haematological cancers, where they act as either oncogenes or tumour suppressors depending on cellular context. Through targeting of oncogenic signalling cascades such as Wnt/β-catenin, TGFβ/Smad and Hippo pathways, miR-181s influence metastatic dissemination and chemosensitivity. Their dysregulation in cancer stem cells further underscores a role in tumour initiation and therapeutic resistance. Translational efforts have explored miR-181 mimics and inhibitors as novel agents to restore tumour suppressive networks or to blunt oncogenic drivers, while circulating miR-181 levels are under investigation as minimally invasive biomarkers for patient stratification and treatment monitoring.

Research from Nature Portfolio

Recent investigations have demonstrated the therapeutic potential of modulating miR-181b in acute leukaemia, where treatment with a natural flavonoid was shown to suppress miR-181b-5p, trigger ATM activation and induce apoptosis via intrinsic and extrinsic pathways. In non-small cell lung cancer, restoration of miR-181b enhanced cisplatin chemosensitivity and reduced metastatic behaviour by directly targeting components of the TGFβR1/Smad signalling axis, highlighting a chemosensitising strategy. Foundational work in glioblastoma multiforme revealed that elevated miR-181 expression reverses mesenchymal transition, inhibits invasive growth through suppression of nuclear transport factors and correlates with improved patient survival across large genomic cohorts.

MicroRNA-181 Family in Cancer Biology and Therapeutics publication trend

The graph below shows the total number of articles in microrna-181 family in cancer biology and therapeutics across all publications each year (not limited to Nature Index journals).

Technical terms

microRNA (miRNA): Short noncoding RNA molecule that regulates gene expression by binding to messenger RNA and inhibiting its translation or promoting degradation.

Apoptosis: Programmed cell death characterised by specific morphological and biochemical features, essential for tissue homeostasis and elimination of damaged cells.

Epithelial–mesenchymal transition (EMT): Biological process by which epithelial cells acquire mesenchymal properties, enhancing migratory capacity and invasiveness.

Chemosensitivity: Degree to which cancer cells respond to chemotherapeutic agents, influencing treatment efficacy.

Signal transduction: Series of molecular events by which cells convert extracellular cues into intracellular responses, often mediated by kinases and transcription factors.

References

1. The Role of the MiR-181 Family in Hepatocellular Carcinoma. Cells (2024).
2. miR-181b-5p/SOCS2/JAK2/STAT5 axis facilitates the metastasis of hepatoblastoma. Precision Clinical Medicine (2023).
3. Pinostrobin, a fingerroot compound, regulates miR-181b-5p and induces acute leukemic cell apoptosis. Scientific Reports (2023).
4. MiR-181b regulates cisplatin chemosensitivity and metastasis by targeting TGFβR1/Smad signaling pathway in NSCLC. Scientific Reports (2015).
5. Upregulation of miR-181s reverses mesenchymal transition by targeting KPNA4 in glioblastoma. Scientific Reports (2015).
6. The Pervasive Role of the miR-181 Family in Development, Neurodegeneration, and Cancer. International Journal of Molecular Sciences (2020).
7. Identification of microRNA‐181 by genome‐wide screening as a critical player in EpCAM–positive hepatic cancer stem cells. Hepatology (2009).
8. MicroRNA-181a promotes angiogenesis in colorectal cancer by targeting SRCIN1 to promote the SRC/VEGF signaling pathway. Cell Death & Disease (2018).