Role of microRNA in epithelial to mesenchymal transition and metastasis and clinical perspectives
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Cites background from "Role of microRNA in epithelial to m..."
...DNA methylation is a relatively stable epigenetic modification that mediates silencing of repetitive elements and certain gene promoters [52]....
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...Abnormal patterns of genomic methylation in cancer are characterized by global losses of genomic methylation and hypermethylation, predominantly in CpG islands, a well-recognized epigenetic event in cancer [52]....
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258 citations
References
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"Role of microRNA in epithelial to m..." refers background in this paper
...A near-perfect match of the seed and the 3′ UTR mRNA sequence leads to mRNA degradation; whereas, partial complementation results in reduced expression by either mRNA removal or translation impairment.(3,5) Thus, a single miRNA might affect the expression of several mRNA targets, even within the same signaling pathway, and simultaneously control diverse biological processes, including differentiation, proliferation, migration, or cell survival....
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11,624 citations
"Role of microRNA in epithelial to m..." refers background in this paper
...To date, approximately 700 human miRNAs have been identified, and it is estimated that more than 30% of the global mRNA expression is regulated by the miRNAs.(1) The miRNAs are either localized within introns, sharing promoter regulation with the host gene, or endowed with their own independent promoters and transcriptional regulation....
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9,470 citations
"Role of microRNA in epithelial to m..." refers background in this paper
...Interestingly, poorly differentiated carcinomas present an overall decrease of total miRNA expression, suggesting a role for the miRNAs in the regulation of different mechanisms governing epithelial plasticity.(25) Targeting the EMT-TFs’ modulators or the EMTTFs themselves, pivotal proteins implicated in invasion and migration, and/or regulatory enzymes involved in miRNA biosynthesis constitutes the most common mechanism used by the miRNAs to regulate epithelial plasticity and, hence, promote or inhibit metastatic tumor progression....
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8,642 citations
"Role of microRNA in epithelial to m..." refers background in this paper
...Several of these EMT-TFs are thereby considered EMT drivers, and their expression is directly correlated with poor outcome.(16,17,21) EMT-TFs from the SNAIL, ZEB, and TWIST families govern EMT through a complex EMT-TF network, which entails a strong transcriptional control...
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...Up to 90% of human tumors are carcinomas, which originate from the differenti- ated epithelium and are susceptible to suffer an EMT process within certain tumor subpopulations in response to external cues.19–21 The hallmarks of the EMT program are the loss of E-cadherin and apical–basal cell polarity, accompanied by the gain of mesenchymal characteristics, including the acquisition of cell migration and invasion abilities, as well as an increased expression of mesenchymal markers, such as vimentin, fibronectin, and N-cadherin.17 The molecular and cellular mechanisms underlying an EMT are complex and can be initiated by multiple extracellular signals that finally activate transcription factors, miRNAs, and/or differ- ent signaling pathways, depending on the physiological or pathological contexts....
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...However, there is growing evidence that at least three additional regulatory levels solidly support the EMT/ MET programs in parallel – miRNA expression, differential splicing, and translational and posttranslational control – that affect localization and protein stability.(14,17,18) In this review, we will discuss the most relevant recent findings concerning epithelial plasticity regulation by miRNA expression....
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...The hallmarks of the EMT program are the loss of E-cadherin and apical–basal cell polarity, accompanied by the gain of mesenchymal characteristics, including the acquisition of cell migration and invasion abilities, as well as an increased expression of mesenchymal markers, such as vimentin, fibronectin, and N-cadherin.(17) The molecular and cellular mechanisms underlying an EMT are complex and can be initiated by multiple extracellular signals that finally activate transcription factors, miRNAs, and/or different signaling pathways, depending on the physiological or pathological contexts....
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8,052 citations
"Role of microRNA in epithelial to m..." refers result in this paper
...Conversely, ZEB1 represses miR-183 and miR-203 which, in turn, target BMI1 and other stemness factors, such as SOX2 and KLF4,(47) which support previous studies that showed that EMT confers cell stemness properties.(48,49) Importantly, the EMT-stemness association is also found in vivo in basal-like breast tumors, a subtype of breast cancer associated with poor differentiation grade, enriched in numerous EMT, and stemness markers....
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