scholarly journals The Role of Circular RNAs in Keratinocyte Carcinomas

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4240
Author(s):  
Thomas Meyer ◽  
Michael Sand ◽  
Lutz Schmitz ◽  
Eggert Stockfleth
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Rna Molecules ◽  
Factors Associated ◽  
New Therapeutic Approaches ◽  
Non Coding Rna ◽  
Micro Rnas ◽  
Pubmed Search

Keratinocyte carcinomas (KC) include basal cell carcinomas (BCC) and cutaneous squamous cell carcinomas (cSCC) and represents the most common cancer in Europe and North America. Both entities are characterized by a very high mutational burden, mainly UV signature mutations. Predominately mutated genes in BCC belong to the sonic hedgehog pathway, whereas, in cSCC, TP53, CDKN2A, NOTCH1/2 and others are most frequently mutated. In addition, the dysregulation of factors associated with epithelial to mesenchymal transition (EMT) was shown in invasive cSCC. The expression of factors associated with tumorigenesis can be controlled in several ways and include non-coding RNA molecules, such as micro RNAs (miRNA) long noncoding RNAs (lncRNA) and circular RNAs (circRNA). To update findings on circRNA in KC, we reviewed 13 papers published since 2016, identified in a PubMed search. In both BCC and cSCC, numerous circRNAs were identified that were differently expressed compared to healthy skin. Some of them were shown to target miRNAs that are also dysregulated in KC. Moreover, some studies confirmed the biological functions of individual circRNAs involved in cancer development. Thus, circRNAs may be used as biomarkers of disease and disease progression and represent potential targets of new therapeutic approaches for KC.

scholarly journals Oncogenic Role of Exosomal Circular and Long Noncoding RNAs in Gastrointestinal Cancers

2022 ◽  
Vol 23 (2) ◽  
pp. 930
Author(s):  
Ba Da Yun ◽  
Ye Ji Choi ◽  
Seung Wan Son ◽  
Gabriel Adelman Cipolla ◽  
Fernanda Costa Brandão Berti ◽  
...  
Keyword(s):  
Epithelial To Mesenchymal Transition ◽  
Cell Communication ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Circular Rnas ◽  
Gastrointestinal Cancers ◽  
Gastrointestinal Malignancies ◽  
Mesenchymal Transition ◽  
Novel Therapeutic Strategies

Circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) are differentially expressed in gastrointestinal cancers. These noncoding RNAs (ncRNAs) regulate a variety of cellular activities by physically interacting with microRNAs and proteins and altering their activity. It has also been suggested that exosomes encapsulate circRNAs and lncRNAs in cancer cells. Exosomes are then discharged into the extracellular environment, where they are taken up by other cells. As a result, exosomal ncRNA cargo is critical for cell–cell communication within the cancer microenvironment. Exosomal ncRNAs can regulate a range of events, such as angiogenesis, metastasis, immune evasion, drug resistance, and epithelial-to-mesenchymal transition. To set the groundwork for developing novel therapeutic strategies against gastrointestinal malignancies, a thorough understanding of circRNAs and lncRNAs is required. In this review, we discuss the function and intrinsic features of oncogenic circRNAs and lncRNAs that are enriched within exosomes.

scholarly journals Epithelial to Mesenchymal Transition: A Mechanism that Fuels Cancer Radio/Chemoresistance

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 428 ◽  
Author(s):  
József Dudás ◽  
Andrea Ladányi ◽  
Julia Ingruber ◽  
Teresa Bernadette Steinbichler ◽  
Herbert Riechelmann
Keyword(s):  
T Cells ◽  
Transcription Factors ◽  
Tumor Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Protein Translation ◽  
Therapy Resistance ◽  
Mesenchymal Transition ◽  
Rna Molecules ◽  
Tumor Microenvironments ◽  
Micro Rnas

Epithelial to mesenchymal transition (EMT) contributes to tumor progression, cancer cell invasion, and therapy resistance. EMT is regulated by transcription factors such as the protein products of the SNAI gene family, which inhibits the expression of epithelial genes. Several signaling pathways, such as TGF-beta1, IL-6, Akt, and Erk1/2, trigger EMT responses. Besides regulatory transcription factors, RNA molecules without protein translation, micro RNAs, and long non-coding RNAs also assist in the initialization of the EMT gene cluster. A challenging novel aspect of EMT research is the investigation of the interplay between tumor microenvironments and EMT. Several microenvironmental factors, including fibroblasts and myofibroblasts, as well as inflammatory, immune, and endothelial cells, induce EMT in tumor cells. EMT tumor cells change their adverse microenvironment into a tumor friendly neighborhood, loaded with stromal regulatory T cells, exhausted CD8+ T cells, and M2 (protumor) macrophages. Several EMT inhibitory mechanisms are instrumental in reversing EMT or targeting EMT cells. Currently, these mechanisms are also significant for clinical use.

scholarly journals LncRNA TUG1 promotes the progression of colorectal cancer via the miR-138-5p/ZEB2 axis

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Zhenkun Yan ◽  
Miaomiao Bi ◽  
Qiyu Zhang ◽  
Yumei Song ◽  
Sen Hong
Keyword(s):  
Colorectal Cancer ◽  
Epithelial To Mesenchymal Transition ◽  
Area Under The Curve ◽  
Luciferase Reporter ◽  
Mesenchymal Transition ◽  
Diagnosis And Prognosis ◽  
Non Coding Rna ◽  
Tissue Specimens

Abstract To explore the role of long-chain non-coding RNA (lncRNA) taurine up-regulated gene 1 (TUG1) in the development of colorectal cancer (CRC) via the miR-138-5p/zinc finger E-box-binding homeobox 2 (ZEB2) axis. Eighty-four CRC tissue specimens and 84 corresponding paracancerous tissue specimens were sampled from 84 patients with CRC admitted to the First Hospital of Jilin University from January 2018 to September 2019. The TUG1 expression in the specimens was determined, and its value in diagnosis and prognosis of CRC was analyzed. Additionally, constructed stable and transient overexpresison vectors and inhibition vectors were transfected into CRC cells. The MTT, transwell, and flow cytometry were adopted for analysis on the proliferation, invasion, and apoptosis of transfected cells, respectively, and a dual luciferase reporter (DLR) assay was carried out for correlation determination between TUG1 and miR-138-5p and between miR-138-5p and ZEB2. TUG1 was up-regulated in CRC, and serum TUG1 could be adopted as a diagnostic marker of CRC, with area-under-the-curve (AUC) larger than 0.8. In addition, siRNA-TUG1, shRNA-TUG1, miR-138-5p-mimics, and miR-138-5p-inhibitor were transfected into cells, and it turned out that overexpressing miR-138-5p and inhibiting ZEB2 exerted the same effects. The DLR assay revealed that TUG1 was able to targetedly regulate miR-138-5p, and miR-138-5p could targetedly regulate ZEB2, and in vitro experiments revealed that TUG1 could affect the epithelial-to-mesenchymal transition (EMT) of CRC via the miR-138-5p/ZEB2 axis. TUG1 could promote the development of CRC via the miR-138-5p/ZEB2 axis.

scholarly journals Exosome-Mediated Signaling in Epithelial to Mesenchymal Transition and Tumor Progression

2018 ◽  
Vol 8 (1) ◽  
pp. 26 ◽  
Author(s):  
Alice Conigliaro ◽  
Carla Cicchini
Keyword(s):  
Tumor Progression ◽  
Intercellular Communication ◽  
Epithelial To Mesenchymal Transition ◽  
Current Knowledge ◽  
Cell Communication ◽  
Therapeutic Approaches ◽  
Mesenchymal Transition ◽  
Rna Molecules ◽  
Dna And Rna

Growing evidence points to exosomes as key mediators of cell–cell communication, by transferring their specific cargo (e.g., proteins, lipids, DNA and RNA molecules) from producing to receiving cells. In cancer, the regulation of the exosome-mediated intercellular communication may be reshaped, inducing relevant changes in gene expression of recipient cells in addition to microenvironment alterations. Notably, exosomes may deliver signals able to induce the transdifferentiation process known as Epithelial-to-Mesenchymal Transition (EMT). In this review, we summarize recent findings on the role of exosomes in tumor progression and EMT, highlighting current knowledge on exosome-mediated intercellular communication in tumor-niche establishment, migration, invasion, and metastasis processes. This body of evidence suggests the relevance of taking into account exosome-mediated signaling and its multifaceted aspects to develop innovative anti-tumoral therapeutic approaches.

scholarly journals Exosomal microRNAs and other non-coding RNAs as colorectal cancer biomarkers: a review

Mutagenesis ◽  
2019 ◽  
Vol 35 (3) ◽  
pp. 243-260 ◽  
Author(s):  
Antonio Francavilla ◽  
Szimonetta Turoczi ◽  
Sonia Tarallo ◽  
Pavel Vodicka ◽  
Barbara Pardini ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Expression Profiles ◽  
Predictive Markers ◽  
Circular Rnas ◽  
Rna Molecules ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Prognostic And Predictive Markers

Abstract The circulating human transcriptome, which includes both coding and non-coding RNA (ncRNA) molecules, represents a rich source of potential biomarkers for colorectal cancer (CRC) that has only recently been explored. In particular, the release of RNA-containing extracellular vesicles (EVs), in a multitude of different in vitro cell systems and in a variety of body fluids, has attracted wide interest. The role of RNA species in EVs is still not fully understood, but their capacity to act as a form of distant communication between cells and their higher abundance in association with cancer demonstrated their relevance. In this review, we report the evidence from both in vitro and human studies on microRNAs (miRNAs) and other ncRNA profiles analysed in EVs in relation to CRC as diagnostic, prognostic and predictive markers. The studies so far highlighted that, in exosomes, the most studied category of EVs, several miRNAs are able to accurately discriminate CRC cases from controls as well as to describe the progression of the disease and its prognosis. Most of the time, the in vitro findings support the miRNA profiles detected in human exosomes. The expression profiles measured in exosomes and other EVs differ and, interestingly, there is a variability of expression also among different subsets of exosomes according to their proteic profile. On the other hand, evidence is still limited for what concerns exosome miRNAs as early diagnostic and predictive markers of treatment. Several other ncRNAs that are carried by exosomes, mostly long ncRNAs and circular RNAs, seem also to be dysregulated in CRC. Besides various technical challenges, such as the standardisation of EVs isolation methods and the optimisation of methodologies to characterise the whole spectrum of RNA molecules in exosomes, further studies are needed in order to elucidate their relevance as CRC markers.

scholarly journals Investigating the Underlying Mechanisms of Circular RNAs and Their Application in Clinical Research of Cervical Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Jian Liu ◽  
He Zhu ◽  
Li Fu ◽  
Tianmin Xu
Keyword(s):  
Cervical Cancer ◽  
Rna Binding ◽  
Regulation Of Gene Expression ◽  
Rna Binding Protein ◽  
Circular Rnas ◽  
Rna Molecules ◽  
Innovative Strategies ◽  
Non Coding Rna ◽  
Underlying Mechanisms

Circular RNAs (circRNAs) are non-coding RNA molecules, and these are differentially expressed in various diseases, including cancer, suggesting that circRNAs can regulate certain diseases. CircRNAs can act as miRNAs sponges, RNA-binding protein (RBP) sponges, and translation regulators, and they can become an important part of the regulation of gene expression. Furthermore, because of their biomedical features in body fluids, such as high abundance, conservation, and stability, circRNAs are seen as potential biomarkers for various cancers. Cervical cancer (CC) is one of the main causes of cancer-related death in women, and there have been a large number of studies that analyze circRNAs as a new object to be evaluated in CC. Therefore, this review, by understanding the role of circRNAs in CC, may create innovative strategies in the future clinical diagnosis, treatment, and prognosis of CC and promote the development of personalized and highly accurate cancer therapy.

The role of DUBs in the post-translational control of cell migration

2019 ◽  
Vol 63 (5) ◽  
pp. 579-594 ◽  
Author(s):  
Guillem Lambies ◽  
Antonio García de Herreros ◽  
Víctor M. Díaz
Keyword(s):  
Cell Migration ◽  
Translational Control ◽  
Epithelial To Mesenchymal Transition ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Mesenchymal Transition ◽  
Tgfβ Receptors ◽  
Fundamental Process ◽  
Multistep Process

Abstract Cell migration is a multifactorial/multistep process that requires the concerted action of growth and transcriptional factors, motor proteins, extracellular matrix remodeling and proteases. In this review, we focus on the role of transcription factors modulating Epithelial-to-Mesenchymal Transition (EMT-TFs), a fundamental process supporting both physiological and pathological cell migration. These EMT-TFs (Snail1/2, Twist1/2 and Zeb1/2) are labile proteins which should be stabilized to initiate EMT and provide full migratory and invasive properties. We present here a family of enzymes, the deubiquitinases (DUBs) which have a crucial role in counteracting polyubiquitination and proteasomal degradation of EMT-TFs after their induction by TGFβ, inflammatory cytokines and hypoxia. We also describe the DUBs promoting the stabilization of Smads, TGFβ receptors and other key proteins involved in transduction pathways controlling EMT.

scholarly journals The Role of Extracellular Vesicles as Shuttles of RNA and Their Clinical Significance as Biomarkers in Hepatocellular Carcinoma

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 902
Author(s):  
Eva Costanzi ◽  
Carolina Simioni ◽  
Gabriele Varano ◽  
Cinzia Brenna ◽  
Ilaria Conti ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Extracellular Vesicles ◽  
Tumor Metastasis ◽  
Biological Processes ◽  
Rna Molecules ◽  
Expression Of Genes ◽  
Non Coding Rna ◽  
Donor Cells ◽  
Relevant Role

Extracellular vesicles (EVs) have attracted interest as mediators of intercellular communication following the discovery that EVs contain RNA molecules, including non-coding RNA (ncRNA). Growing evidence for the enrichment of peculiar RNA species in specific EV subtypes has been demonstrated. ncRNAs, transferred from donor cells to recipient cells, confer to EVs the feature to regulate the expression of genes involved in differentiation, proliferation, apoptosis, and other biological processes. These multiple actions require accuracy in the isolation of RNA content from EVs and the methodologies used play a relevant role. In liver, EVs play a crucial role in regulating cell–cell communications and several pathophysiological events in the heterogeneous liver class of cells via horizontal transfer of their cargo. This review aims to discuss the rising role of EVs and their ncRNAs content in regulating specific aspects of hepatocellular carcinoma development, including tumorigenesis, angiogenesis, and tumor metastasis. We analyze the progress in EV-ncRNAs’ potential clinical applications as important diagnostic and prognostic biomarkers for liver conditions.

scholarly journals The Role of Autophagy and lncRNAs in the Maintenance of Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1239
Author(s):  
Leila Jahangiri ◽  
Tala Ishola ◽  
Perla Pucci ◽  
Ricky M. Trigg ◽  
Joao Pereira ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cancer Progression ◽  
Regulatory Networks ◽  
Epithelial To Mesenchymal Transition ◽  
Tumour Microenvironment ◽  
Repair Capacity ◽  
Mesenchymal Transition ◽  
Cellular Processes

Cancer stem cells (CSCs) possess properties such as self-renewal, resistance to apoptotic cues, quiescence, and DNA-damage repair capacity. Moreover, CSCs strongly influence the tumour microenvironment (TME) and may account for cancer progression, recurrence, and relapse. CSCs represent a distinct subpopulation in tumours and the detection, characterisation, and understanding of the regulatory landscape and cellular processes that govern their maintenance may pave the way to improving prognosis, selective targeted therapy, and therapy outcomes. In this review, we have discussed the characteristics of CSCs identified in various cancer types and the role of autophagy and long noncoding RNAs (lncRNAs) in maintaining the homeostasis of CSCs. Further, we have discussed methods to detect CSCs and strategies for treatment and relapse, taking into account the requirement to inhibit CSC growth and survival within the complex backdrop of cellular processes, microenvironmental interactions, and regulatory networks associated with cancer. Finally, we critique the computationally reinforced triangle of factors inclusive of CSC properties, the process of autophagy, and lncRNA and their associated networks with respect to hypoxia, epithelial-to-mesenchymal transition (EMT), and signalling pathways.

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