MicroRNA Modulation in Glioblastoma Pathogenesis

Glioblastoma represents the most aggressive primary brain tumour in adults, marked by rapid proliferation, diffuse invasion and pronounced molecular heterogeneity. Central to its pathogenesis is the dysregulation of microRNAs—short non-coding RNA molecules that fine-tune gene expression by binding target messenger RNAs. Aberrant microRNA expression in glioblastoma influences key hallmarks of cancer, including evasion of apoptosis, enhanced migratory and invasive capacity, angiogenesis and resistance to chemotherapy and radiotherapy. MicroRNA networks intersect with epigenetic programmes such as DNA methylation and histone modifications, linking genetic and environmental cues to transcriptional outcomes. The blood–brain barrier and the complex tumour microenvironment pose significant challenges for delivery of microRNA-based therapeutics, yet advances in smart delivery systems and multi-targeting approaches are opening new avenues. A detailed understanding of microRNA-mediated regulatory circuits is critical for the development of diagnostic biomarkers, prognostic signatures and novel interventions aimed at re-establishing normal regulatory balance within glioblastoma cells.

Research from Nature Portfolio

Recent studies have employed an integrative multi-omics strategy to unravel mechanisms of microRNA dysregulation in lower-grade glioma, providing insights transferable to high-grade glioblastoma. By combining genome-wide analyses of DNA methylation, copy number variation and microRNA expression, four molecular subtypes with distinct prognoses and immune-related features were defined. Construction of a microRNA regulatory network pinpointed specific microRNAs that drive tumour heterogeneity and promote immune evasion. Functional validation confirmed that selected microRNAs enhance glioma cell migration, invasion and proliferation, highlighting their potential both as stratification biomarkers and as targets to bolster immunotherapy responses in aggressive gliomas.

MicroRNA Modulation in Glioblastoma Pathogenesis publication trend

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

Technical terms

microRNA: Short non-coding RNA molecule (~22 nucleotides) that regulates gene expression by base-pairing with target mRNAs.

Glioblastoma: Grade IV malignant brain tumour characterised by rapid growth, diffuse infiltration and genetic heterogeneity.

Epigenetic modification: Heritable change in gene expression without alteration of DNA sequence, including DNA methylation and histone modification.

Copy number variation: Genomic alteration involving duplication or deletion of DNA segments that can affect gene dosage and expression.

Immune evasion: Strategies by which tumour cells avoid detection or destruction by the host immune system.

References

1. Engineered smart materials for RNA based molecular therapy to treat Glioblastoma. Bioactive Materials (2023).
2. A diagnostic circulating miRNA signature as orchestrator of cell invasion via TKS4/TKS5/EFHD2 modulation in human gliomas. Journal of Experimental & Clinical Cancer Research (2023).
3. Identification of a miRNA multi-targeting therapeutic strategy in glioblastoma. Cell Death & Disease (2023).
4. MicroRNAs in adult high-grade gliomas: Mechanisms of chemotherapeutic resistance and their clinical relevance. Biomedicine & Pharmacotherapy (2024).
5. Integrative analysis of genomic and epigenomic regulation reveals miRNA mediated tumor heterogeneity and immune evasion in lower grade glioma. Communications Biology (2024).