DIO3, the thyroid hormone inactivating enzyme, promotes tumorigenesis and metabolic reprogramming in high grade serous ovarian cancer

Moskovich, Dotan; Alfandari, Adi; Finkelshtein, Yael; Weisz, Avivit; Katzav, Aviva; Kidron, Debora; Edelstein, E. L.; Veroslavski, Daniel; Perets, Ruth; Arbib, Nissim; Kadan, Yfat; Fishman, Ami; Lerer, Bernard; Ellis, Martin; Ashur‐Fabian, Osnat

doi:10.1016/j.canlet.2020.11.011

Cited by 10 publications

(6 citation statements)

References 45 publications

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“…For example, Zhao et al [10] have shown that mitochondrial elongation factor 2 (MIEF2) overexpression promotes growth and metastasis in ovarian cancer by reprogramming glucose metabolism. The knockdown of DIO3 in high-grade serous ovarian cancer leads to a decrease in the Warburg effect and carcinogenic signal transduction and tumor growth inhibition [11]. By reversing the Warburg effect, ABT737, a B cell lymphoma (BCL2) inhibitor, promotes H 2 O 2 -induced apoptosis and increases the antitumor effect of oxidative stress, sensitizing ovarian cancer cells to chemotherapy [12].…”

Section: Discussionmentioning

confidence: 99%

Establishment of a novel glycolysis-related prognostic gene signature for ovarian cancer and its relationships with immune infiltration of the tumor microenvironment

Pan

et al. 2021

J Transl Med

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Background Glycolysis affects tumor growth, invasion, chemotherapy resistance, and the tumor microenvironment. In this study, we aimed to construct a glycolysis-related prognostic model for ovarian cancer and analyze its relationship with the tumor microenvironment’s immune cell infiltration. Methods We obtained six glycolysis-related gene sets for gene set enrichment analysis (GSEA). Ovarian cancer data from The Cancer Genome Atlas (TCGA) database and two Gene Expression Omnibus (GEO) datasets were divided into two groups after removing batch effects. We compared the tumor environments' immune components in high-risk and low-risk groups and analyzed the correlation between glycolysis- and immune-related genes. Then, we generated and validated a predictive model for the prognosis of ovarian cancer using the glycolysis-related genes. Results Overall, 27/329 glycolytic genes were associated with survival in ovarian cancer, 8 of which showed predictive value. The tumor cell components in the tumor microenvironment did not differ between the high-risk and low-risk groups; however, the immune score differed significantly between groups. In total, 13/24 immune cell types differed between groups, including 10 T cell types and three other immune cell types. Eight glycolysis-related prognostic genes were related to the expression of multiple immune-related genes at varying degrees, suggesting a relationship between glycolysis and immune response. Conclusions We identified eight glycolysis-related prognostic genes that effectively predicted survival in ovarian cancer. To a certain extent, the newly identified gene signature was related to the tumor microenvironment, especially immune cell infiltration and immune-related gene expression. These findings provide potential biomarkers and therapeutic targets for ovarian cancer.

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Section: Discussionmentioning

confidence: 99%

Establishment of a novel glycolysis-related prognostic gene signature for ovarian cancer and its relationships with immune infiltration of the tumor microenvironment

Pan

et al. 2021

J Transl Med

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“…This might be due to the suppression of FSH-induced action of aromatase, caused by THs. Some studies documented similar results, while a few others reported contradictory results [5,14]. The definite mechanism by which thyroid hormones regulate gonadotropins is not well-established.…”

Section: Discussionmentioning

confidence: 99%

“…However, hyperthyroidism and ovarian cancer have been associated more recently, and it has been observed that hyperthyroidism increases levels of deiodinase type 3, which then promotes cancer proliferation. Deiodinase type 3 has been found in high-grade serous ovarian cancer (HGSOC) samples of human patients [14]. The effect of thyroid-stimulating hormone (TSH) on induced egg development may have been altered by the thyroid-stimulating hormone receptor/cyclic AMP (TSHR/cAMP), TSHR expression level signaling cascade in granulosa cells [15].…”

Section: Introductionmentioning

confidence: 99%

The Interplay Between Hyperthyroidism and Ovarian Cytoarchitecture in Albino Rats

Mahmud¹,

Khan²,

Saad³

2021

Cureus

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BackgroundHyperthyroid females often complain of menstrual disturbances and impaired fertility. This study was designed to observe the effect of hyperthyroidism on ovarian folliculogenesis and the hypophyseal-gonadal axis. MethodologyAdult female Wistar albino rats (n= 12), six to eight weeks of age, and weighing 70-162 g, were divided randomly into control (Group A) and experimental (Group B) groups. Group A received daily intraperitoneal injections of 250 µL normal saline (10 µL 5 µM NaOH dissolved in it) for 14 days. Group B received a daily intraperitoneal injection of levothyroxine (600 µg/kg body weight) to induce hyperthyroidism. Rats were weighed at the start and the end of the experimental period on the day of sacrifice. ResultsStatistical analysis of the data revealed successful induction of hyperthyroidism in Group B as their thyroidstimulating hormone (TSH) levels decreased significantly. The ovarian size was significantly reduced in the hyperthyroid group (p < 0.029). There was a significant decrease in thickness of the ovarian capsule (p < 0.000), an increase in the number of primordial, primary, and secondary follicles (p < 0.001, 0.000, and 0.001, respectively), and a decrease in size of primary and secondary follicles (p < 0.041 and 0.020) in the hyperthyroid group. ConclusionHyperthyroidism can affect ovarian cytoarchitecture, probably by acting directly on its receptors and thus affects female fertility.

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“…In addition, hypoxia induces DIO3 translocation to the nucleus through interaction with the heat shock protein 40 (Hsp40), thus enabling deiodination of T3 at the site of its interaction with the genome [ 324 ]. These events are deleterious in cancers, such as ovarian cancer and hepatocellular carcinoma, in which THs act as oncosuppressors [ 325 , 326 ].…”

Section: Thyroid Hormones and Brain Cancermentioning

confidence: 99%

Involvement of Thyroid Hormones in Brain Development and Cancer

Schiera

Liegro

2021

Cancers

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The development and maturation of the mammalian brain are regulated by thyroid hormones (THs). Both hypothyroidism and hyperthyroidism cause serious anomalies in the organization and function of the nervous system. Most importantly, brain development is sensitive to TH supply well before the onset of the fetal thyroid function, and thus depends on the trans-placental transfer of maternal THs during pregnancy. Although the mechanism of action of THs mainly involves direct regulation of gene expression (genomic effects), mediated by nuclear receptors (THRs), it is now clear that THs can elicit cell responses also by binding to plasma membrane sites (non-genomic effects). Genomic and non-genomic effects of THs cooperate in modeling chromatin organization and function, thus controlling proliferation, maturation, and metabolism of the nervous system. However, the complex interplay of THs with their targets has also been suggested to impact cancer proliferation as well as metastatic processes. Herein, after discussing the general mechanisms of action of THs and their physiological effects on the nervous system, we will summarize a collection of data showing that thyroid hormone levels might influence cancer proliferation and invasion.

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DIO3, the thyroid hormone inactivating enzyme, promotes tumorigenesis and metabolic reprogramming in high grade serous ovarian cancer

Cited by 10 publications

References 45 publications

Establishment of a novel glycolysis-related prognostic gene signature for ovarian cancer and its relationships with immune infiltration of the tumor microenvironment

Establishment of a novel glycolysis-related prognostic gene signature for ovarian cancer and its relationships with immune infiltration of the tumor microenvironment

The Interplay Between Hyperthyroidism and Ovarian Cytoarchitecture in Albino Rats

Involvement of Thyroid Hormones in Brain Development and Cancer

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