Differential regulation of monocarboxylate transporter 8 expression in thyroid cancer and hyperthyroidism

Badziong, Julia; Ting, Saskia; Synoracki, S.; Tiedje, Vera; Brix, Klaudia; Brabant, Georg; Moeller, Lars C.; Schmid, Kurt Werner; Führer, Dagmar; Zwanziger, Denise

doi:10.1530/eje-17-0279

Cited by 16 publications

(15 citation statements)

References 19 publications

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“…Of the 1,098 mRNAs that were significantly differentially expressed in thyroid cancer, GO functional enrichment analysis showed that these genes were mainly enriched in the plasma membrane. Interestingly, several previous studies have shown that a large number of genes located in the plasma membrane have roles in thyroid cancer [15,16]. In this analysis, 101 differentially expressed mRNAs were shown to be related with OS, and these results were consistent with several previous reports, confirming the associations of some of these genes with prognosis.…”

Section: Discussionsupporting

confidence: 91%

Identification of RNA Expression Profiles in Thyroid Cancer to Construct a Competing Endogenous RNA (ceRNA) Network of mRNAs, Long Noncoding RNAs (lncRNAs), and microRNAs (miRNAs)

Chen

Yang

et al. 2019

Med Sci Monit

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BackgroundThe aims of this study were to use RNA expression profile bioinformatics data from cases of thyroid cancer from the Cancer Genome Atlas (TCGA), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and the Gene Ontology (GO) databases to construct a competing endogenous RNA (ceRNA) network of mRNAs, long noncoding RNAs (lncRNAs), and microRNAs (miRNAs).Material/MethodsTCGA provided RNA profiles from 515 thyroid cancer tissues and 56 normal thyroid tissues. The DESeq R package analyzed high-throughput sequencing data on differentially expressed RNAs. GO and KEGG pathway analysis used the DAVID 6.8 and the ClusterProfile R package. Kaplan-Meier survival statistics and Cox regression analysis were performed. The thyroid cancer ceRNA network was constructed based on the miRDB, miRTarBase, and TargetScan databases.ResultsThere were 1,098 mRNAs associated with thyroid cancer; 101 mRNAs were associated with overall survival (OS). Multivariate analysis developed a risk scoring system that identified seven signature mRNAs, with a discriminative value of 0.88, determined by receiver operating characteristic (ROC) curve analysis. A ceRNA network included 13 mRNAs, 31 lncRNAs, and seven miRNAs. Four out of the 31 lncRNAs and all miRNAs were down-regulated, and the remaining RNAs were upregulated. Two lncRNAs (MIR1281A2HG and OPCML-IT1) and one miRNA (miR-184) were significantly associated with OS in patients with thyroid cancer.ConclusionsDifferential RNA expression profiling in thyroid cancer was used to construct a ceRNA network of mRNAs, lncRNAs, and miRNAs that showed potential in evaluating prognosis.

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Section: Discussionsupporting

confidence: 91%

Identification of RNA Expression Profiles in Thyroid Cancer to Construct a Competing Endogenous RNA (ceRNA) Network of mRNAs, Long Noncoding RNAs (lncRNAs), and microRNAs (miRNAs)

Chen

Yang

et al. 2019

Med Sci Monit

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“…Strikingly, the gene expression of MCT12 is most frequently downregulated in tumors compared with non‐neoplastic tissues in the examined cancer entities. Only few genomewide gene expression profiling studies are available, indicating altered expression of MCT isoforms e.g., in hepatocellular carcinoma,38 thyroid cancer,39 adrenocortical cancer,40 or ovarian cancer41 but the precise molecular mechanisms behind altered MCT expression are not revealed. Given that tumor growth is a highly energy consuming process and tumors demonstrate metabolic reprogramming and considerable metabolic plasticity, other MCT isoforms presumably play an important role in cancer development and progression as suppliers of nutrients or exporters of metabolic end products.…”

Section: Mcts In Cancermentioning

confidence: 99%

Clinical and Functional Relevance of the Monocarboxylate Transporter Family in Disease Pathophysiology and Drug Therapy

Fisel

Schaeffeler

Schwab

2018

Clinical Translational Sci

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The solute carrier (SLC) SLC16 gene family comprises 14 members and encodes for monocarboxylate transporters (MCTs), which mediate the absorption and distribution of monocarboxylic compounds across plasma membranes. As the knowledge about their physiological function, activity, and regulation increases, their involvement and contribution to cancer and other diseases become increasingly evident. Moreover, promising opportunities for therapeutic interventions by directly targeting their endogenous functions or by exploiting their ability to deliver drugs to specific organ sites emerge.

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“…Thus, there is a need to characterize protein abundance as a closer proxy for physiological relevance (30). This is particularly important given that previous studies showed dynamic changes in mRNA expression that are dependent on TH axis status (25,(31)(32)(33), sex (34), and fasting conditions (35,36), during critical illness (24,37) and throughout development (38,39). Studies investigating MCT8 protein expression are still limited due to a lack of specific antibodies and difficulties in obtaining human brain tissue for immunostaining (3).…”

Section: Introductionmentioning

confidence: 99%

Spatiotemporal Changes of Cerebral Monocarboxylate Transporter 8 Expression

Wilpert

Krueger

Opitz

et al. 2020

Thyroid

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Background: Mutations of monocarboxylate transporter 8 (MCT8), a thyroid hormone (TH)-specific transmembrane transporter, cause a severe neurodevelopmental disorder, the Allan-Herndon-Dudley syndrome. In MCT8 deficiency, TH is not able to reach those areas of the brain where TH uptake depends on MCT8. Currently, therapeutic options for MCT8-deficient patients are missing, as TH treatment is not successful in improving neurological deficits. Available data on MCT8 protein and transcript levels indicate complex expression patterns in neural tissue depending on species, brain region, sex, and age. However, information on human MCT8 expression is still scattered and additional efforts are needed to map sites of MCT8 expression in neurovascular units and neural tissue. This is of importance because new therapeutic strategies for this disease are urgently needed. Methods: To identify regions and time windows of MCT8 expression, we used highly specific antibodies against MCT8 to perform immunofluorescence labeling of postnatal murine brains, adult human brain tissue, and human cerebral organoids. Results: Qualitative and quantitative analyses of murine brain samples revealed stable levels of MCT8 protein expression in endothelial cells of the blood-brain barrier (BBB), choroid plexus epithelial cells, and tanycytes during postnatal development. Conversely, the neuronal MCT8 protein expression that was robustly detectable in specific brain regions of young mice strongly declined with age. Similarly, MCT8 immunoreactivity in adult human brain tissue was largely confined to endothelial cells of the BBB. Recently, cerebral organoids emerged as promising models of human neural development and our first analyses of forebrain-like organoids revealed MCT8 expression in early neuronal progenitor cell populations. Conclusions: With respect to MCT8-deficient conditions, our analyses not only strongly support the contention that the BBB presents a lifelong barrier to TH uptake but also highlight the need to decipher the TH transport role of MCT8 in early neuronal cell populations in more detail. Improving the understanding of the spatiotemporal expression in latter barriers will be critical for therapeutic strategies addressing MCT8 deficiency in the future.

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Differential regulation of monocarboxylate transporter 8 expression in thyroid cancer and hyperthyroidism

Cited by 16 publications

References 19 publications

Identification of RNA Expression Profiles in Thyroid Cancer to Construct a Competing Endogenous RNA (ceRNA) Network of mRNAs, Long Noncoding RNAs (lncRNAs), and microRNAs (miRNAs)

Identification of RNA Expression Profiles in Thyroid Cancer to Construct a Competing Endogenous RNA (ceRNA) Network of mRNAs, Long Noncoding RNAs (lncRNAs), and microRNAs (miRNAs)

Clinical and Functional Relevance of the Monocarboxylate Transporter Family in Disease Pathophysiology and Drug Therapy

Spatiotemporal Changes of Cerebral Monocarboxylate Transporter 8 Expression

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