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Toward precision oncology: deciphering the circRNA-EMT axis in cancer and its therapeutic implications
Zekai Lv1, Guang Xie2, Wenming Xu1
1Joint Lab of Reproductive Medicine of SCU-CUHK, Lab of Reproductive Genetics and Epigenetics, Department of Obstetrics/Gynecology, Key Laboratory of Birth Defects and Related Disease of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, China.
Abstract:
The epithelial-mesenchymal transition is a pivotal driver of cancer metastasis, the leading cause of mortality in solid tumours. Circular RNAs, a unique class of endogenous RNAs characterized by covalently closed loop structures and high stability, have emerged as key regulators in this process. Accumulating evidence reveals widespread dysregulation of circRNAs during EMT, where they function as critical modulators - either promoting or inhibiting the metastatic cascade. This review systematically elucidates the mechanisms by which circRNAs govern EMT, focusing on their interactions with classical signalling pathways (TGF-β, Wnt/β-catenin, and PI3K/AKT) and core EMT-transcription factors. Furthermore, we evaluate the dual promise of circRNAs as stable, disease-specific biomarkers for liquid biopsy and as novel therapeutic targets. Deciphering the complex circRNA-EMT regulatory network not only deepens our understanding of metastasis but also provides a rational framework for developing precision oncology strategies to intercept metastatic disease.
Insights
Circular RNAs (circRNAs) regulate epithelial-mesenchymal transition (EMT), a key process in cancer metastasis. Understanding circRNA-EMT interactions offers new strategies for cancer biomarker and therapy development.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Epithelial-mesenchymal transition (EMT) drives cancer metastasis and mortality in solid tumors.
- Circular RNAs (circRNAs) are stable RNA molecules that regulate gene expression.
- CircRNAs are increasingly recognized as crucial regulators of EMT.
Purpose of the Study:
- To systematically review the mechanisms by which circRNAs regulate EMT.
- To explore circRNA interactions with key signaling pathways and transcription factors in EMT.
- To evaluate circRNAs as biomarkers and therapeutic targets for metastatic cancer.
Main Methods:
- Literature review of studies on circRNAs and EMT.
- Analysis of circRNA interactions with TGF-β, Wnt/β-catenin, and PI3K/AKT pathways.
- Examination of circRNA roles in conjunction with EMT-transcription factors.
Main Results:
- CircRNAs are dysregulated during EMT and act as promoters or inhibitors of metastasis.
- CircRNAs modulate EMT through interactions with major signaling cascades.
- CircRNAs offer potential as biomarkers for liquid biopsy and as therapeutic targets.
Conclusions:
- CircRNAs play a significant role in governing EMT and cancer metastasis.
- The circRNA-EMT regulatory network provides insights into metastasis mechanisms.
- CircRNAs represent promising avenues for precision oncology and anti-metastasis strategies.
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