Esteller, A* Dotaz Zobrazit nápovědu
Since the first demonstration of microRNA (miRNA) roles in tumorigenesis, a multitude of studies have established a solid scaffold that supports the increased and accelerated progression in this field. The aim of this article is to comment on the most recent findings of miRNAs in cancer, particularly focusing on epigenetics and the potential clinical applications derived from comprehensive and exhaustive research carried out during the last years. RECENT FINDINGS: A global reduction of miRNA levels is emerging as a common hallmark of cancer. Several strands of evidence have shown that one of the mechanisms responsible for this deregulation is the epigenetic silencing of miRNA genes. In turn, recent studies have revealed that some miRNAs directly repress enzymes of the epigenetic machinery, including DNA methyltransferases, histone deacetylases and histone methyltransferases. These facts broaden the promising biomedical uses of miRNAs. Apart from epigenetic mechanisms, other causes of miRNA deregulation in cancer are also discussed in this review, as well as novel clinical applications of miRNAs in cancer treatment. SUMMARY: The ability of individual miRNAs to regulate multiple target genes, implicated in turn in several pathways, confers them an extraordinary capacity as multifunctional tools for cancer therapy. Thus, restoration of the level of a single or few pleiotropic miRNAs could eventually re-establish molecular pathways altered in cancer, providing a more effective therapeutic strategy. However, further studies will be needed to validate the preliminary successful results of miRNA-based therapy obtained in cellular and animal models. Also, it is crucial to expand our knowledge about the molecular regulation of the miRNome (global miRNA expression levels) in physiological and pathological settings.
- MeSH
- antimetabolity antitumorózní MeSH
- azacytidin farmakologie metabolismus terapeutické užití MeSH
- chemorezistence genetika MeSH
- deoxycytidin farmakologie metabolismus terapeutické užití MeSH
- epigeneze genetická účinky léků MeSH
- inhibitory enzymů farmakologie metabolismus terapeutické užití MeSH
- lidé MeSH
- metylace DNA * genetika účinky léků MeSH
- nádory farmakoterapie genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Personalised medicine (PM) presents a great opportunity to improve the future of individualised healthcare. Recent advances in -omics technologies have led to unprecedented efforts characterising the biology and molecular mechanisms that underlie the development and progression of a wide array of complex human diseases, supporting further development of PM. This article reflects the outcome of the 2021 EATRIS-Plus Multi-omics Stakeholder Group workshop organised to 1) outline a global overview of common promises and challenges that key European stakeholders are facing in the field of multi-omics research, 2) assess the potential of new technologies, such as artificial intelligence (AI), and 3) establish an initial dialogue between key initiatives in this space. Our focus is on the alignment of agendas of European initiatives in multi-omics research and the centrality of patients in designing solutions that have the potential to advance PM in long-term healthcare strategies.
- Publikační typ
- časopisecké články MeSH
While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04-1.15, p = 1.9 x 10(-4) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03-1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.
- MeSH
- alfa receptor estrogenů metabolismus MeSH
- antigeny CD44 genetika MeSH
- aurora kinasa A genetika MeSH
- extracelulární matrix - proteiny genetika MeSH
- genetická predispozice k nemoci genetika MeSH
- genetické lokusy genetika MeSH
- geny BRCA1 * MeSH
- geny BRCA2 * MeSH
- jaderné proteiny genetika MeSH
- jednonukleotidový polymorfismus MeSH
- karcinogeneze genetika MeSH
- lidé MeSH
- mléčné žlázy lidské metabolismus MeSH
- molekulární evoluce MeSH
- mutace * MeSH
- nádory prsu enzymologie genetika patologie MeSH
- pravděpodobnostní funkce MeSH
- proteiny asociované s mikrotubuly genetika MeSH
- proteiny buněčného cyklu genetika MeSH
- retrospektivní studie MeSH
- tubulin genetika MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, N.I.H., Intramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
