Molecular and Cellular Insights into the Development of Uterine Fibroids
Abstract
:1. Introduction
2. Uterine Leiomyoma Etiopathology
2.1. Hormone Features
2.2. Genetics
2.2.1. Inherited Susceptibility
2.2.2. Point Mutations
2.2.3. Chromosomal Abnormalities
- Chromothripsis
- Target genes of chromosomal alterations
2.3. Epigenetics
2.4. Cell Origin
3. Molecular Tools in Clinical Management of Uterine Leiomyomas
3.1. Detection–Putative Biomarkers
3.2. Classification–Gene Expression Profiling
3.3. Treatment–Targetable Dysregulated Pathways
3.3.1. Wnt/β-Catenin Pathway
3.3.2. PI3K/AKT Pathway
3.3.3. TGF-β Pathway
4. Clinical Translation and Future Research
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Molecular Tools in the Clinical Management of uLM | Detection: Putative biomarkers | ↑ serum levels in uLM | Biomarkers for differential diagnosis | ||||
• Leptin | • CA125 | • AOPP | • GDF-15 | ||||
• VEGF | • Vitamin D3 | • LRG1 | • CA125 | ||||
• Ghrelin | • TGF-β | • YKL40 | • HLA-G | ||||
Classification: Gene expression profiling | Molecular subclassification | Differential diagnosis | |||||
Mutational status of driver genes | uLM versus uterine leiomyosarcoma | ||||||
Similar cellular processes involved | Clearly distinct transcriptomic profiles | ||||||
• MED12 | High number of genes involved | ||||||
• HMGA2 | • BRCA2 | • FOXM1 | • PAX3 | ||||
Treatment: Targetable pathways | WNT-β catenin pathway | PI3K-AKT pathway | TGFβ pathway | ||||
↑ proliferation | ↑ growth | Overexpression of cytokines | |||||
↑ stem cell function | Involved in development | ↑ growth | |||||
Inhibited by vitamin D3 | Inhibited by GnRH analogues and UPA | Inhibited by GnRH analogues and UPA |
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Machado-Lopez, A.; Simón, C.; Mas, A. Molecular and Cellular Insights into the Development of Uterine Fibroids. Int. J. Mol. Sci. 2021, 22, 8483. https://doi.org/10.3390/ijms22168483
Machado-Lopez A, Simón C, Mas A. Molecular and Cellular Insights into the Development of Uterine Fibroids. International Journal of Molecular Sciences. 2021; 22(16):8483. https://doi.org/10.3390/ijms22168483
Chicago/Turabian StyleMachado-Lopez, Alba, Carlos Simón, and Aymara Mas. 2021. "Molecular and Cellular Insights into the Development of Uterine Fibroids" International Journal of Molecular Sciences 22, no. 16: 8483. https://doi.org/10.3390/ijms22168483