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Small Interfering RNAs, MicroRNAs, and NPs in Gynecological Cancers
Published in Loutfy H. Madkour, Nanoparticle-Based Drug Delivery in Cancer Treatment, 2022
Recent studies have revealed that the levels of miRNAs are associated with the prognosis of gynecologic malignancies. He et al. compared the levels of miR-944 in 68 EC tissues vs. 20 normal endometrial specimens [232]. They identified miR-944 to be consistently up-regulated in EC tissues, and clinicopathological studies suggested high level of miR-944 association with FIGO stages and pathology classification of EC. Further, Kaplan–Meier analysis suggested that patients exhibiting high miR-944 have a shorter survival time. Zuberi et al. examined the association of miR-200a, miR-200b, and miR-200c with clinicopathological factors and progression of OC [487]. They identified an association of miR-200a and miR-200c with disease progression. miR-200a alone was associated with tumor stage and histology, while high level of miR-200c in patients was associated with lymph node metastasis [487].
Epigenetic and Metabolic Alterations in Cancer Cells: Mechanisms and Therapeutic Approaches
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2020
Emerging work on FH- and SDH-mutant cancers have shed insights into the downstream pathways affected by epigenetic dysregulation. Using integrative genomic and proteomic analysis, Sciacovelli et al. (Sciacovelli and Frezza, 2017; Sciacovelli et al., 2016) demonstrated that fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition (EMT) in renal cancer. Loss of FH was found to induce hypermethylation of the promoter region of miR-200ba429 cluster, leading to their epigenetic suppression. As a result, miR-200 target genes, such as EMT-related transcription factors ZEB1 and ZEB2, are de-repressed, eliciting downstream signaling cascades that induce cancer invasion and metastasis. Fumarate supplementation phenocopies the effect of FH loss even in cells that express wildtype FH, an effect that is reversed by a-ketoglutarate, suggesting imbalance of these metabolites is sufficient to drive EMT in cancer. Inactivating FH mutations are also thought to promote oncogenesis by suppressing histone demethylation. Sulkowski et al. (2018) reported that fumarate and succinate are suppressors of the homologous recombination (HR) DNA-repair pathway, leading to elevated levels of DNA double stranded breaks (DSBs) in tumors with FH or SDH mutations. Mechanistically, accumulation of fumarate and succinate in FH or SDH mutant tumors inhibit histone demethylases KDM4A and KDM4B, as indicated by the elevated H3K36me3 and H3K9me3 levels. Ectopic expression of KDM5A/KDM5B, or supplementation with a-ketoglutarate in cancer cell lines rescued the DSB phenotype in FH or SDH mutant cancer cell lines, indicating that overproduction of succinate/ fumarate mediate DSBs via direct blockade of KDM5A/KDM5B activity. Collectively, abnormal levels of fumarate/succinate contribute to tumorigenesis as a consequence of the altered DNA and histone methylation profiles.
The expression of microRNAs and exposure to environmental contaminants related to human health: a review
Published in International Journal of Environmental Health Research, 2022
Maria Rosaria Tumolo, Alessandra Panico, Antonella De Donno, Pierpaolo Mincarone, Carlo Giacomo Leo, Roberto Guarino, Francesco Bagordo, Francesca Serio, Adele Idolo, Tiziana Grassi, Saverio Sabina
Accumulated evidence suggests that the bladder epithelium may be one of the primary targets of As-induced carcinogenesis. Michailidi et al. analyzed urine samples from subjects exposed to different levels of As, showing miR-200c-3p and miR-205-5p inversely associated with As exposure compared to unexposed controls. Moreover, the authors validated the expression of these miRNAs in urine samples from patients with urothelial carcinoma in comparison with controls without cancer. The results displayed a low expression of miR-205-5p, suggesting its potential use as biomarker for bladder cancer (Michailidi et al. 2015). Both miR-200c-3p and miR-205-5p have tumour suppressive functions. miR-200c-3p can reverse epithelial-mesenchymal transition via regulation of zinc finger E-box-binding homeobox 1 (ZEB1) and ZEB2 (Wellner et al. 2009). Hence, these miRNAs may play a role in the tumour initiation and progression.
Atmospheric fine particulate matter and epithelial mesenchymal transition in pulmonary cells: state of the art and critical review of the in vitro studies
Published in Journal of Toxicology and Environmental Health, Part B, 2020
Margaux Cochard, Frédéric Ledoux, Yann Landkocz
MicroRNA are also involved in EMT, notably the miR200 family. The miRNA binds to mRNA inhibiting translation of proteins. miR200 family inhibits induction of EMT by targeting ZEB1 and ZEB2. Other miRNA are involved in EMT including miR-9 and miR-30a and target the principal transcription factors SNAI and ZEB, but also miR-10b and miR-21 which promote invasion and migration through inhibition of several other proteins (Zhang and Ma 2012).