Expression Profiling of a Human Thyroid Cell Line Stably Expressing the BRAFV600E Mutation

Kim, Byoung Ae; Jee, Hyeon Gun; Yi, Jin Wook; Kim, Su Jin; Chai, Young Jun; Choi, June Young; Lee, Kyu Eun

doi:10.21873/cgp.20018

Cited by 15 publications

(15 citation statements)

References 39 publications

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“…As demonstrated by in vitro our experiments, Cav-1 mRNA and protein were strongly decreased in response to IL-1β/IFN-γ in Nthy-ori 3-1 cells. Nthy-ori 3-1 cells, an immortalized thyroid follicular epithelial cell line, are highly suitable for studies of the control of growth and function in the human thyroid [37,38]. Our results are consistent with previous reports that a combination of IL-1α and IFN-γ induces Cav-1 reduction in primary cultures of human thyrocytes [18,39].…”

Section: Discussionsupporting

confidence: 92%

Caveolin-1 regulates autophagy activity in thyroid follicular cells and is involved in Hashimoto’s thyroiditis disease

Luo

Mao

et al. 2018

Endocr J

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Hashimoto's thyroiditis (HT) is considered a T helper-type 1 (Th1) cytokine-dominant autoimmune thyroid disease. Caveolin-1 (Cav-1), a part of the thyroxisome multiprotein complex, is localized at the apical pole of thyrocytes and is indispensable for synthesis of thyroid hormones and modulation of oxidative stress in order to avoid cell damage and apoptosis. Reduced autophagy induces thyroid follicular cells (TFC) apoptosis by activating reactive oxygen species (ROS) in HT patients. Nevertheless, whether Cav-1 has roles in the regulation of autophagy remains largely unclear. In this study, we examined Th1 cytokines and Cav-1 expression in HT thyroid tissues, determined the effects of interleukin-1beta (IL-1β) and interferon-gamma (IFN-γ) on Cav-1 and autophagy activity in TFC, and investigated the association between Cav-1 and autophagy activity in vitro. Our results indicate that higher levels of IL-1β and IFN-γ and lower levels of Cav-1 were expressed in thyroid tissues of HT patients than in those of normal controls. Cav-1 mRNA and protein levels were significantly decreased in TFC exposed to IL-1β and IFN-γ, accompanied by decreased expression of autophagy-related protein LC3B-II. Interestingly, small interfering RNA (siRNA)-mediated Cav-1 knockdown in TFC reduced LC3B-II protein expression. Taken together, these results suggest that lack of Cav-1 expression inhibited autophagy activity in TFC exposed to Th1 cytokines (IL-1β and IFN-γ), which might be a novel pathogenetic mechanism of HT.

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Section: Discussionsupporting

confidence: 92%

Caveolin-1 regulates autophagy activity in thyroid follicular cells and is involved in Hashimoto’s thyroiditis disease

Luo

Mao

et al. 2018

Endocr J

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“…G0S2 promotes apoptosis by interacting with BCL2 and by preventing the formation of protective BCL2 and BAX heterodimers [ 39 ]. Kim et al have demonstrated that the G0S2 gene is significantly upregulated in BRAF V600E cells compared to wild-type BRAF human thyroid cells, and this expression change caused by the BRAF V600E mutation may have an important role in thyroid cancer development [ 42 ]. These observations are consistent with our results, demonstrating that G0S2 downregulation is related to the suppression of glioma cell invasion ( Fig 3 ).…”

Section: Discussionmentioning

confidence: 99%

Methylation dependent down-regulation of G0S2 leads to suppression of invasion and improved prognosis of IDH1-mutant glioma

et al. 2018

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Isocitrate dehydrogenase (IDH) mutations are a prognostic factor in diffuse glioma. However, the mechanism by which these mutations improve prognosis are not clear. In a subset of IDH-mutant glioma, remodeling of the methylome results in the glioma-CpG island methylator phenotype (G-CIMP) and transcriptional reorganization. In this study, we focus on G0/G1 switch 2 (G0S2), which is highly downregulated in G-CIMP glioma. We found that G0S2 expression tended to increase as the WHO grade increased, and G0S2 knockdown inhibited glioma invasion. Additionally, we revealed that the overexpression of the DNA demethylase Ten-eleven translocation 2 (TET2) in IDH1-plasmid transfected glioblastoma multiforme (GBM) cells restored G0S2 expression. These results indicate that G0S2 is epigenetically silenced in IDH1-mutant glioma. In addition, the stereotactic delivery of glioma cells with decreased G0S2 expression in the mouse brain resulted in prolonged survival. The Cancer Genome Atlas (TCGA) analysis also indicated that survival is longer in the lower G0S2 expression group than in the higher G0S2 expression group. Moreover, G0S2 expression was higher in recurrent tumor specimens than at the initial diagnosis in the same patient. These results provide one explanation for the improved survival in IDH1-mutant glioma as well as a new epigenetic target for glioma treatment.

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“…Nthy-ori 3-1 is an immortalized thyroid follicular epithelial cell line derived from normal adult thyroid tissue, and Nthy-ori 3-1 cell clones expressing either wild-type BRAF (Nthy/WT) or mutant BRAF (Nthy/V600E) were established (Kim et al 2017). BCPAP and MDA-T32, the human PTC cell lines harboring both BRAF V600E and TERT promoter mutations, were kindly provided by Dr Minho Shong (Chungnam National University, Daejon, Korea) and purchased from the American Type Culture Collection, respectively.…”

Section: Cell Culturementioning

confidence: 99%

Interaction of BRAF-induced ETS factors with mutant TERT promoter in papillary thyroid cancer

Song

Yoo

Kim

et al. 2019

Endocrine-Related Cancer

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Synergistic effects of BRAFV600E and TERT promoter mutations on the poor clinical outcomes in papillary thyroid cancer (PTC) have been demonstrated. The potential mechanism of this phenomenon has been proposed: MAPK pathway activation by the BRAFV600E mutation may upregulate E-twenty six (ETS) transcription factors, increasing TERT expression by binding to the ETS-binding site generated by the TERT promoter mutation; however, it has not yet been fully proven. This article provides transcriptomic insights into the interaction between BRAFV600E and TERT promoter mutations mediated by ETS factors in PTC. RNA sequencing data on 266 PTCs from The Cancer Genome Atlas and 65 PTCs from our institute were analyzed for gene expression changes and related molecular pathways, and the results of transcriptomic analyses were validated by in vitro experiments. TERT mRNA expression was increased by the coexistence of BRAFV600E and TERT promoter mutations (fold change, 16.17; q-value = 7.35 × 10−12 vs no mutation). In the ETS family of transcription factors, ETV1, ETV4 and ETV5 were upregulated by the BRAFV600E/MAPK pathway activation. These BRAFV600E-induced ETS factors selectively bound to the mutant TERT promoter. The molecular pathways activated by BRAFV600E were further augmented by adding the TERT promoter mutation, and the pathways related to immune responses or adhesion molecules were upregulated by TERT expression. The mechanism of the synergistic effect between BRAFV600E and TERT promoter mutations on cancer invasiveness and progression in PTC may be explained by increased TERT expression, which may result from the BRAF-induced upregulation of several ETS transcription factors.

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Expression Profiling of a Human Thyroid Cell Line Stably Expressing the BRAFV600E Mutation

Abstract: Abstract. Background

Cited by 15 publications

References 39 publications

Caveolin-1 regulates autophagy activity in thyroid follicular cells and is involved in Hashimoto’s thyroiditis disease

Caveolin-1 regulates autophagy activity in thyroid follicular cells and is involved in Hashimoto’s thyroiditis disease

Methylation dependent down-regulation of G0S2 leads to suppression of invasion and improved prognosis of IDH1-mutant glioma

Interaction of BRAF-induced ETS factors with mutant TERT promoter in papillary thyroid cancer

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