Abstract
Epithelial–mesenchymal transition (EMT) is a fundamental physiologically relevant process that occurs during morphogenesis and organ development. In a pathological setting, the transition from epithelial toward mesenchymal cell phenotype is hijacked by cancer cells, allowing uncontrolled metastatic dissemination. The competing endogenous RNA (ceRNA) hypothesis proposes a competitive environment resembling a large-scale regulatory network of gene expression circuits where alterations in the expression of both protein-coding and non-coding genes can make relevant contributions to EMT progression in cancer. The complex regulatory diversity is exerted through an array of diverse epigenetic factors, reaching beyond the transcriptional control that was previously thought to single-handedly govern metastatic dissemination. The present review aims to unravel the competitive relationships between naturally occurring ceRNA transcripts for the shared pool of the miRNA-200 family, which play a pivotal role in EMT related to cancer dissemination. Upon acquiring more knowledge and clinical evidence on non-genetic factors affecting neoplasia, modulation of the expression levels of diverse ceRNAs may allow for the development of novel prognostic/diagnostic markers and reveal potential targets for the disruption of cancer-related EMT.
Highlights
Primary tumor development is a histopathological progression involving the welldocumented acquisition of a series of somatic mutations [1,2]
Coupling epithelial–mesenchymal transition (EMT)-TFs exclusively to pathogenic de-differentiation might not always be accurate as these TFs bear broader physiologically relevant roles. With this in mind, compelling data suggests that a disturbance in the balance between different regulatory networks resulting in a shift from epithelial to mesenchymal cell phenotype is one of the essential prerequisites allowing for the invasion–metastasis cascade, differentiating it from the physiologically relevant EMT
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) Long non-coding RNA molecules (lncRNAs) molecule is one of the most commonly implicated lncRNA molecules in various types of cancer; Xiao et al further defined its role as an oncogene, acting through sponging of multiple miR-200 family members, resulting in ZEB2 increase
Summary
Primary tumor development is a histopathological progression involving the welldocumented acquisition of a series of somatic mutations [1,2]. Relevant, hoping to understand cancer dissemination by acknowledging somatic mutations accumulating in the genome of neoplastic cells and defining the genes and gene products that drive the process bears limitations. While mutations in driver genes do facilitate the development of pro-metastatic traits, the baffling complexity of the mechanism seems to originate from crosstalk between regulatory networks. The recent revelation that less than 2% of the human genome is related to protein-coding genes has emphasized the importance of unravelling these networks beyond frontline transcriptional control in order to fully comprehend cancer dissemination [3]. We set out to examine the dynamics of the main intrinsic regulatory mechanisms governing cancer-related epithelial–mesenchymal transition (EMT) and identify the stoichiometry of vital players in the competing endogenous (ceRNA) network with a focus on cancer progression and metastasis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
