miRNA Expression in Anaplastic Thyroid Carcinomas

Hebrant, Aline; Floor, Sebastien; Saiselet, Manuel; Antoniou, Aline; Desbuleux, Alice; Snyers, Bérengère; La, Caroline; Aubain, Nicolas De Saint; Leteurtre, Emmanuelle; Andry, Guy; Maenhaut, Carine

doi:10.1371/journal.pone.0103871

Cited by 40 publications

(38 citation statements)

References 41 publications

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“…Restored expression of miR-30a in a mouse model resulted in smaller metastases but did not affect the tumor growth (81). The role of the miR-30 family in the pathogenesis of ATC was additionally supported in a study by Hebrant et al (82), which also identified miR-29a as the second regulator of the LOX gene. Novel studies identified other microRNAs, miR-21 (83) and miR-4295 (84), as potential oncomiRs in ATC.…”

Section: The Potential Of Micrornas In Thyroid Cancer Treatmentmentioning

confidence: 85%

MECHANISMS IN ENDOCRINOLOGY: MicroRNA in diagnostics and therapy of thyroid cancer

Wójcicka

Kolanowska

Jażdżewski

2016

European Journal of Endocrinology

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MicroRNAs, short non-coding regulators of the gene expression, are subjects of numerous investigations assessing their potential use in the diagnostics and management of human diseases. In this review, we focus on studies that analyze the utility of microRNAs as novel diagnostic and therapeutic tools in follicular cell-derived thyroid carcinomas. This very interesting and promising field brings new insight into future strategies for personalized medicine.

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Section: The Potential Of Micrornas In Thyroid Cancer Treatmentmentioning

confidence: 85%

MECHANISMS IN ENDOCRINOLOGY: MicroRNA in diagnostics and therapy of thyroid cancer

Wójcicka

Kolanowska

Jażdżewski

2016

European Journal of Endocrinology

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“…They performed extensive validation directed toward alterations in fatty acid metabolism identified by the gene expression study but did not perform gene ontology or pathway clustering. There are also additional genomic or transcriptomic ATC studies leveraging different technologies that have been reported in the literature (22)(23)(24)(25)(26)(27)(28)(29). These were not included, as our methods necessitated using data derived from a single platform.…”

Section: Discussionmentioning

confidence: 99%

Cell Cycle M-Phase Genes Are Highly Upregulated in Anaplastic Thyroid Carcinoma

Weinberger

Ponny

et al. 2017

Thyroid

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Background: Anaplastic thyroid carcinoma (ATC) accounts for only 3% of thyroid cancers, yet strikingly, it accounts for almost 40% of thyroid cancer deaths. Currently, no effective therapies exist. In an effort to identify ATC-specific therapeutic targets, we analyzed global gene expression data from multiple studies to identify ATC-specific dysregulated genes. Methods: The National Center for Biotechnology Information Gene Expression Omnibus database was searched for high-throughput gene expression microarray studies from human ATC tissue along with normal thyroid and/or papillary thyroid cancer (PTC) tissue. Gene expression levels in ATC were compared with normal thyroid or PTC using seven separate comparisons, and an ATC-specific gene set common in all seven comparisons was identified. We investigated these genes for their biological functions and pathways. Results: There were three studies meeting inclusion criteria, (including 32 ATC patients, 69 PTC, and 75 normal). There were 259 upregulated genes and 286 downregulated genes in ATC with at least two-fold change in all seven comparisons. Using a five-fold filter, 36 genes were upregulated in ATC, while 40 genes were downregulated. Of the 10 top globally upregulated genes in ATC, 4/10 (MMP1, ANLN, CEP55, and TFPI2) are known to play a role in ATC progression; however, 6/10 genes (TMEM158, CXCL5, E2F7, DLGAP5, MME, and ASPM) had not been specifically implicated in ATC. Similarly, 3/10 (SFTA3, LMO3, and C2orf40) of the most globally downregulated genes were novel in this context, while 7/10 genes (SLC26A7, TG, TSHR, DUOX2, CDH1, PDE8B, and FOXE1) have been previously identified in ATC. We experimentally validated a significant correlation for seven transcription factors (KLF16, SP3, ETV6, FOXC1, SP1, EGFR1, and MAFK) with the ATC-specific genes using microarray analysis of ATC cell lines. Ontology clustering of globally altered genes revealed that ''mitotic cell cycle'' is highly enriched in the globally upregulated gene set (44% of top upregulated genes, p-value <10 -30 ). Conclusions: By focusing on globally altered genes, we have identified a set of consistently altered biological processes and pathways in ATC. Our data are consistent with an important role for M-phase cell cycle genes in ATC, and may provide direction for future studies to identify novel therapeutic targets for this disease.

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“…64 MicroRNAs are increasingly recognized as important regulators of EMT and of CSCs. [65][66][67][68][69][70] Recent studies have shown that the miR-200 family has a major regulatory role in EMT. 65 The miR-200 family has been shown to regulate EMT induced by EGF/EGFR 66 and also by targeting TGFβR1.…”

Section: Non-coding Rnas and Emt Micrornas And Emtmentioning

confidence: 99%

“…65 The miR-200 family has been shown to regulate EMT induced by EGF/EGFR 66 and also by targeting TGFβR1. 65 Braun et al 65 67 found that specific miRNAs in ATCs had a regulatory role in EMT. They reported that the LOX gene, which is a principal factor in EMT, was an upregulated mRNA target in ATCs associated with downregulation of miR-29a.…”

Section: Non-coding Rnas and Emt Micrornas And Emtmentioning

confidence: 99%

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

Hardin

Zhang

Helein

et al. 2017

Laboratory Investigation

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The cancer stem-like cell (CSC) hypothesis postulates that a small population of cells in a cancer has self-renewal and clonal tumor initiation properties. These cells are responsible for tumor initiation, growth, recurrence and for resistance to chemotherapy and radiation therapy. CSCs can be characterized using markers such as SSEA-1, SSEA-4, CD44, CD24, ALDEFLUOR and others. CSCs form spheres when they are cultured in serum-free condition in low attachment plates and can generate tumors when injected into immune-deficient mice. During epithelial to mesenchymal transition (EMT), cells lose cellular adhesion and polarity and acquire an invasive phenotype. Recent studies have established a relationship between EMT and increased numbers of CSCs in some solid malignancies. Non-coding RNAs such as microRNAs and long non-coding RNAs (lncRNAs) have been shown to have important roles during EMT and some of these molecules also have regulatory roles in the proliferation of CSCs. Specific lncRNAs enhanced cell migration and invasion in breast carcinomas, which was associated with the generation of stem cell properties. The tumor microenvironment of CSCs also has an important role in tumor progression. Recent studies have shown that the interaction between tumor cells and the local microenvironment at the metastatic site leads to the development of premetastatic niche(s) and allows for the proliferation of the metastatic cells during colonization. The role of exosomes in the microenvironment during the EMT program is currently a major area of research. This review examines CSCs and the relationship between EMT and CSCs in solid tumors with emphasis on thyroid CSCs. The role of non-coding RNAs and of the microenvironment in EMT and in tumor progression are also examined. This review also highlights the growing number of studies that show the close association of EMT and CSCs and the role of exosomes and other elements of the tissue microenvironment in CSC metastasis. A better understanding of these mechanisms will lead to more effective targeting of primary and metastatic malignancies.

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miRNA Expression in Anaplastic Thyroid Carcinomas

Cited by 40 publications

References 41 publications

MECHANISMS IN ENDOCRINOLOGY: MicroRNA in diagnostics and therapy of thyroid cancer

MECHANISMS IN ENDOCRINOLOGY: MicroRNA in diagnostics and therapy of thyroid cancer

Cell Cycle M-Phase Genes Are Highly Upregulated in Anaplastic Thyroid Carcinoma

The evolving concept of cancer stem-like cells in thyroid cancer and other solid tumors

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