Regulatory Mechanisms of RNA-Binding Proteins in Cancer

RNA-binding proteins (RBPs) orchestrate multiple layers of post-transcriptional gene regulation that are critical in oncogenesis, tumour progression and metastasis. By recognising sequence or structural motifs—often within the 3′-untranslated regions (3′UTRs) of target transcripts—RBPs can govern mRNA stability, alternative splicing, subcellular localisation and translation efficiency. In parallel, many RBPs participate in microRNA (miRNA) biogenesis, modulating the maturation of miRNA precursors and thus indirectly shaping entire gene-regulatory networks. Post-translational modifications of RBPs, such as phosphorylation or SUMOylation, further fine-tune their interactions with RNA and protein partners, integrating signalling pathways with RNA metabolism. Dysregulation of these mechanisms can drive aberrant expression of oncogenes and tumour suppressors, promote epithelial–mesenchymal transition (EMT) and alter the tumour microenvironment (TME), culminating in enhanced proliferation, invasion and immune evasion. Recent advances have illuminated how specific RBPs contribute to DNA damage responses, cell-cycle control and chemotherapeutic resistance, revealing new opportunities for therapeutic targeting of RBP-mediated circuits in diverse cancer types.

Research from Nature Portfolio

Recent studies have shown that suppression of the KH-type splicing regulatory protein (KHSRP) in aggressive breast cancer cells leads to widespread alterations in both gene expression and alternative splicing profiles. In vitro silencing of KHSRP reduces proliferation, migration and invasion while increasing apoptosis, coinciding with downregulation of key cell-cycle and DNA repair genes (including CCNA2, CDK1 and ERCC1) and dysregulation of splicing events in factors such as PARK7 and UBE2A. These findings underscore a direct role for RBPs in coordinating DNA damage response pathways and suggest that targeting splicing regulators may potentiate chemotherapeutic efficacy. Earlier foundational work revealed that another RBP, KSRP, controls the biogenesis of miR-129 to modulate RUNX1 levels during myeloid cell fate decisions. Although described in developmental contexts, this miRNA-mediated axis also has implications for leukaemogenesis, as RUNX1 is frequently altered in haematological malignancies. Together, these reports highlight how RBPs integrate transcriptional and post-transcriptional networks to influence tumour cell behaviour and lineage-specific oncogenic programmes.

Regulatory Mechanisms of RNA-Binding Proteins in Cancer publication trend

The graph below shows the total number of articles in regulatory mechanisms of rna-binding proteins in cancer across all publications each year (not limited to Nature Index journals).

Technical terms

RNA-binding protein (RBP): A protein that recognises and binds RNA sequences or structures to regulate post-transcriptional gene expression.

AU-rich element (ARE): A sequence motif rich in adenine and uracil nucleotides, often located in the 3′UTR and targeted by RBPs for mRNA decay or stabilisation.

3′-untranslated region (3′UTR): The segment of mRNA downstream of the coding sequence that contains regulatory motifs influencing mRNA stability and translation.

MicroRNA (miRNA): A small non-coding RNA that guides silencing complexes to target mRNAs, leading to translational repression or degradation.

Alternative splicing: The process by which exons of a pre-mRNA are differentially joined or skipped, generating multiple transcript isoforms from a single gene.

Epithelial–mesenchymal transition (EMT): A cellular programme in which epithelial cells acquire mesenchymal traits, enhancing motility and invasiveness in cancer.

Tumour microenvironment (TME): The complex milieu of stromal cells, immune cells, extracellular matrix and signalling factors surrounding tumour cells.

References

1. KHSRP has oncogenic functions and regulates the expression and alternative splicing of DNA repair genes in breast cancer MDA-MB-231 cells. Scientific Reports (2024).
2. KSRP specifies monocytic and granulocytic differentiation through regulating miR-129 biogenesis and RUNX1 expression. Nature Communications (2017).
3. The RNA-binding protein KSRP aggravates malignant progression of clear cell renal cell carcinoma through transcriptional inhibition and post-transcriptional destabilization of the NEDD4L ubiquitin ligase. Journal of Biomedical Science (2023).
4. KHSRP knockdown inhibits papillary renal cell carcinoma progression and sensitizes to gemcitabine. Frontiers in Pharmacology (2024).