scholarly journals The Aryl Hydrocarbon Receptor Is Expressed in Thyroid Carcinoma and Appears to Mediate Epithelial-Mesenchymal-Transition

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 145 ◽  
Author(s):  
Sonia Moretti ◽  
Nicole Nucci ◽  
Elisa Menicali ◽  
Silvia Morelli ◽  
Vittorio Bini ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cell Motility ◽  
Aryl Hydrocarbon Receptor ◽  
Cancer Progression ◽  
Target Genes ◽  
Epithelial Mesenchymal Transition ◽  
Receptor Activation ◽  
Mesenchymal Transition ◽  
Aryl Hydrocarbon ◽  
And Migration

Aryl hydrocarbon receptor (AhR) is expected to promote initiation, progression and invasion of cancer cells regulating proliferation, differentiation, gene expression, inflammation, cell motility and migration. Furthermore, an immunosuppressant function of AhR has been recognized. This study evaluated AhR expression and its role in thyroid cancer progression. AhR expression was assessed by qPCR in 107 thyroid cancer samples (90 PTCs, 11 MTCs, 6 ATCs), and by immunohistochemistry in 41 PTCs. To estimate receptor activation, the expression of target genes CYP1A1 and CYP1B1 was measured. AhR functional effects were evaluated in kynurenine-stimulated FTC-133 and BcPap cell lines by analyzing the expression of genes involved in EMT and cell motility. AhR mRNA expression resulted significantly higher in all the analyzed thyroid cancer samples compared to normal thyroid and a statistically significant correlation with CYP1B1 was detected. Kynurenine-stimulated FTC-133 and BcPap showed the activation of a specific AhR-driven EMT program characterized by E-cadherin decrease and SLUG, N-cadherin and fibronectin increase, resulting in boost of cell motility and invasion. This study confirmed the importance of the IDO1-Kyn-AhR pathway in thyroid cancer tumorigenesis, suggesting an AhR pivotal role in mediating an immunosuppressive microenvironment and favoring the acquisition of a mesenchymal phenotype that could promote invasiveness and metastasis.

scholarly journals Hsa_circRNA_102002 facilitates metastasis of papillary thyroid cancer through regulating miR-488-3p/HAS2 axis

2020 ◽  
Author(s):  
Wei Zhang ◽  
Ting Liu ◽  
Tianshu Li ◽  
Xudong Zhao
Keyword(s):  
Thyroid Cancer ◽  
Papillary Thyroid Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Xenograft Model ◽  
Inhibitory Effect ◽  
Circular Rnas ◽  
Papillary Thyroid ◽  
Mesenchymal Transition ◽  
Mouse Xenograft Model ◽  
And Migration

Abstract As important modulators in various physiological processes, circular RNAs (circRNAs) have been increasingly demonstrated in tumors, including papillary thyroid cancer (PTC). Hsa_circRNA_102002 (circ_102002) is a circRNA derived from alternative splicing of ubiquitin-specific peptidase 22 (USP22) transcript, the role of which needs further investigation. Our results suggested the upregulation of circ_102002 in PTC tissues and cells, and its promoting effects on epithelial–mesenchymal transition (EMT) and cell migration. Mechanism studies showed that circ_102002 could sponge microRNA-488-3p (miR-488-3p) and downregulate its expression. The target relationship between miR-488-3p and hyaluronic acid synthetase 2 (HAS2) in PTC was systematically studied. In addition, our results showed that HAS2 overexpression could restore the inhibited cell EMT and migration. Moreover, the inhibitory effect of downregulation of circ_102002 on PTC growth was evaluated in a mouse xenograft model, which involved miR-488-3p and HAS2 regulation. These findings about the signal axis of circ_102002/miR-488-3p/HAS2 may further elucidate the PTC pathogenesis and improve clinical treatment.

scholarly journals ChrXq27.3 miRNA cluster functions in cancer development

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Kosuke Yoshida ◽  
Akira Yokoi ◽  
Yusuke Yamamoto ◽  
Hiroaki Kajiyama
Keyword(s):  
Cancer Progression ◽  
Target Genes ◽  
Epithelial Mesenchymal Transition ◽  
Mature Mirnas ◽  
Mirna Cluster ◽  
Mesenchymal Transition ◽  
Normal Tissues ◽  
Mirna Clusters ◽  
Cancer Tissues ◽  
Encoding Genes

AbstractMicroRNAs (miRNAs) regulate the expression of their target genes post-transcriptionally; thus, they are deeply involved in fundamental biological processes. miRNA clusters contain two or more miRNA-encoding genes, and these miRNAs are usually coexpressed due to common expression mechanisms. Therefore, miRNA clusters are effective modulators of biological pathways by the members coordinately regulating their multiple target genes, and an miRNA cluster located on the X chromosome q27.3 region has received much attention in cancer research recently. In this review, we discuss the novel findings of the chrXq27.3 miRNA cluster in various types of cancer.The chrXq27.3 miRNA cluster contains 30 mature miRNAs synthesized from 22 miRNA-encoding genes in an ~ 1.3-Mb region. The expressions of these miRNAs are usually negligible in many normal tissues, with the male reproductive system being an exception. In cancer tissues, each miRNA is dysregulated, compared with in adjacent normal tissues. The miRNA-encoding genes are not uniformly distributed in the region, and they are further divided into two groups (the miR-506-514 and miR-888-892 groups) according to their location on the genome. Most of the miRNAs in the former group are tumor-suppressive miRNAs that are further downregulated in various cancers compared with normal tissues. miR-506-3p in particular is the most well-known miRNA in this cluster, and it has various tumor-suppressive functions associated with the epithelial–mesenchymal transition, proliferation, and drug resistance. Moreover, other miRNAs, such as miR-508-3p and miR-509-3p, have similar tumor-suppressive effects. Hence, the expression of these miRNAs is clinically favorable as prognostic factors in various cancers. However, the functions of the latter group are less understood. In the latter group, miR-888-5p displays oncogenic functions, whereas miR-892b is tumor suppressive. Therefore, the functions of the miR-888–892 group are considered to be cell type- or tissue-specific.In conclusion, the chrXq27.3 miRNA cluster is a critical regulator of cancer progression, and the miRNAs themselves, their regulatory mechanisms, and their target genes might be promising therapeutic targets.

scholarly journals Expression and Clinical Utility of Transcription Factors Involved in Epithelial–Mesenchymal Transition during Thyroid Cancer Progression

2021 ◽  
Vol 10 (18) ◽  
pp. 4076
Author(s):  
Enke Baldini ◽  
Chiara Tuccilli ◽  
Daniele Pironi ◽  
Antonio Catania ◽  
Francesco Tartaglia ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Thyroid Cancer ◽  
Cancer Progression ◽  
Clinical Utility ◽  
Epithelial Mesenchymal Transition ◽  
Clinicopathological Parameters ◽  
Mrna Levels ◽  
Vimentin Expression ◽  
Mesenchymal Transition ◽  
E Cadherin

The transcription factors involved in epithelial–mesenchymal transition (EMT-TFs) silence the genes expressed in epithelial cells (e.g., E-cadherin) while inducing those typical of mesenchymal cells (e.g., vimentin). The core set of EMT-TFs comprises Zeb1, Zeb2, Snail1, Snail2, and Twist1. To date, information concerning their expression profile and clinical utility during thyroid cancer (TC) progression is still incomplete. We evaluated the EMT-TF, E-cadherin, and vimentin mRNA levels in 95 papillary TC (PTC) and 12 anaplastic TC (ATC) tissues and correlated them with patients’ clinicopathological parameters. Afterwards, we corroborated our findings by analyzing the data provided by a case study of the TGCA network. Compared with normal tissues, the expression of E-cadherin was found reduced in PTC and more strongly in ATC, while the vimentin expression did not vary. Among the EMT-TFs analyzed, Twist1 seems to exert a prominent role in EMT, being significantly associated with a number of PTC high-risk clinicopathological features and upregulated in ATC. Nonetheless, in the multivariate analysis, none of the EMT-TFs displayed a prognostic value. These data suggest that TC progression is characterized by an incomplete EMT and that Twist1 may represent a valuable therapeutic target warranting further investigation for the treatment of more aggressive thyroid cancers.

scholarly journals Osteopontin Expression in Thyroid Cancer: Deciphering EMT-Related Molecular Mechanisms

Biomedicines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1372
Author(s):  
Bruna Prunes Pena Baroni Viana ◽  
Amanda Vitória Pampolha Gomes ◽  
Etel Rodrigues Pereira Gimba ◽  
Luciana Bueno Ferreira
Keyword(s):  
Thyroid Cancer ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Endocrine System ◽  
Good Prognosis ◽  
Thyroid Tumor ◽  
Diagnostic Tools ◽  
Matricellular Protein ◽  
Mesenchymal Transition

Thyroid cancer is the most common tumor arising from the endocrine system and generally presents good prognosis. However, its aggressive subtypes are related to therapeutic resistance and early metastasis. Epithelial–mesenchymal transition (EMT) and its reverse process, the mesenchymal–epithelial transition (MET), are key events mediating cancer progression, including in thyroid cancer. The matricellular protein osteopontin (OPN) has been reported as a master regulator of EMT in many tumor types. Although high OPN expression has been described and associated with important aspects of thyroid cancer progression, there is no clear evidence regarding OPN as a regulator of EMT in thyroid cancer. Thus, taking together the known roles of OPN in the modulation of EMT in cancer and the information reporting the expression of OPN in thyroid tumor progression, this review aims at summarizing and discussing data related to EMT in thyroid cancer and its putative relation to the roles of OPN in the development of thyroid cancer. These data provide new insights into the molecular mechanisms by which OPN could potentially modulate EMT in thyroid tumors, generating evidence for future studies that may contribute to new therapeutic, prognostic and/or diagnostic tools.

scholarly journals The YAP1–NMU Axis Is Associated with Pancreatic Cancer Progression and Poor Outcome: Identification of a Novel Diagnostic Biomarker and Therapeutic Target

Cancers ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 1477 ◽  
Author(s):  
Yoo ◽  
Lee ◽  
Jun ◽  
Noh ◽  
Lee ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Progression ◽  
Target Genes ◽  
Epithelial Mesenchymal Transition ◽  
The Cancer Genome Atlas ◽  
Mesenchymal Transition ◽  
Tumor Group ◽  
Cancer Genome Atlas

Yes-associated protein (YAP)-1 is highly upregulated in pancreatic cancer and associated with tumor progression. However, little is known about the role of YAP1 and related genes in pancreatic cancer. Here, we identified target genes regulated by YAP1 and explored their role in pancreatic cancer progression and the related clinical implications. Analysis of different pancreatic cancer databases showed that Neuromedin U (NMU) expression was positively correlated with YAP1 expression in the tumor group. The Cancer Genome Atlas data indicated that high YAP1 and NMU expression levels were associated with poor mean and overall survival. YAP1 overexpression induced NMU expression and transcription and promoted cell motility in vitro and tumor metastasis in vivo via upregulation of epithelial–mesenchymal transition (EMT), whereas specific inhibition of NMU in cells stably expressing YAP1 had the opposite effect in vitro and in vivo. To define this functional association, we identified a transcriptional enhanced associate domain (TEAD) binding site in the NMU promoter and demonstrated that YAP1–TEAD binding upstream of the NMU gene regulated its transcription. These results indicate that the identified positive correlation between YAP1 and NMU is a potential novel drug target and biomarker in metastatic pancreatic cancer.

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