scholarly journals Tunicamycin promotes metastasis through upregulating endoplasmic reticulum stress induced GRP78 expression in thyroid carcinoma

2020 ◽  
Author(s):  
Guohong Zhao ◽  
Jianqin Kang ◽  
Guanghui Xun ◽  
Jing Wei ◽  
Xiaoguang Wang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Er Stress ◽  
Anaplastic Thyroid Cancer ◽  
Sequencing Data ◽  
Genomic Amplification ◽  
Ecm Remodeling ◽  
Kegg Pathways ◽  
Normal Tissues ◽  
Underlying Mechanisms

Abstract Background: Thyroid cancer (TC) is the most common type of endocrine malignancy tumor and the incidence of it is increasing over years. Conventional surgery, radiotherapy and chemotherapy are difficult to improve the significant effects of it due to aggression and metastasis of poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC), which are regarded as the most malignant type of TC. Glucose-regulated protein (GRP78) is the key molecule of tumor growth, apoptosis and metastasis. However, the underlying mechanisms of GRP78 on TC still require discussion. This study aimed to explore the role of GRP78 and its potential mechanism in TC.Results: GRP78 expression was increased in TC tissues when compared with adjacent normal tissues. Besides, down-regulation of GRP78 significantly inhibited the metastatic and proliferative ability of ATC cells in in vitro studies. In addition, tunicamycin-induced ER stress up-regulated the expression of GRP78, PERK and XBP1 as well as reversed the metastatic ability of GRP78 in ATC cells. Bioinformatics and statistical analysis of gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for RNA-sequencing data from si-GRP78 and si-control showed that GRP78 might regulate the ability of metastasis through extracellular matrix (ECM) remodeling in ATC cells, as well as the expression of ECM components such as COL1A1 and MMP13 were shown to be highly relevant to ATC. The analysis of GEPIA database confirmed high genomic amplification of MMP13 and COL1A1 in TC tissues and showed correlation with TNM stage. Further western blotting analysis showed that MMP13 might be the target of GRP78 in ATC cells and ER stress could activate the expression of MMP13 that was suppressed by the GRP78 depletion.Conclusions: GRP78 acts as an important regulator of metastasis under ER stress. In addition, the function of GRP7 might be mediated by ECM remodeling in ATC cells, implicating it as a therapeutic target in TC.

scholarly journals Tunicamycin promotes metastasis through upregulating endoplasmic reticulum stress indu​ced GRP78 expression in thyroid carcinoma

2020 ◽  
Author(s):  
Guohong Zhao ◽  
Jianqin Kang ◽  
Guanghui Xun ◽  
Jing Wei ◽  
Xiaoguang Wang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Er Stress ◽  
Anaplastic Thyroid Cancer ◽  
Sequencing Data ◽  
Genomic Amplification ◽  
Ecm Remodeling ◽  
Kegg Pathways ◽  
Normal Tissues ◽  
Underlying Mechanisms

Abstract Background: Thyroid cancer (TC) is the most common type of endocrine malignancy and its incidence is increasing over years. Conventional surgery, radiotherapy and chemotherapy are difficult to improve the significant effects of it due to aggression and metastasis of poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC), and these are regarded as the most malignant types of TC. Glucose-regulated protein (GRP78) is the key molecule of tumor growth, apoptosis and metastasis. However, the underlying mechanisms of GRP78 in TC still require discussion. This study aimed to explore the role of GRP78 and its potential mechanism in TC.Results: GRP78 expression was increased in TC tissues when compared with adjacent normal tissues. Besides, down-regulation of GRP78 significantly inhibited the metastatic and proliferative ability of ATC cells in in vitro studies. In addition, tunicamycin-induced ER stress up-regulated the expression of GRP78, PERK and XBP1 as well as reversed the metastatic ability of GRP78 in ATC cells. Bioinformatics and statistical analysis of gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for RNA-sequencing data with regard to si-GRP78 and si-control showed that GRP78 might regulate the ability of metastasis through extracellular matrix (ECM) remodeling in ATC cells, as well as the expression of ECM components such as COL1A1 and MMP13, which were highly relevant to ATC cells. The analysis of GEPIA database confirmed that high genomic amplification of MMP13 and COL1A1 in TC tissues showed correlation with TNM stage. Further western blotting analysis showed that MMP13 might be the target of GRP78 in ATC cells and ER stress could activate the expression of MMP13 that is suppressed by GRP78 depletion.Conclusions: GRP78 acts as an important regulator of metastasis under ER stress. In addition, the function of GRP78 might be mediated by ECM remodeling in ATC cells, implicating it as a therapeutic target in TC.

scholarly journals Tunicamycin promotes metastasis through upregulating endoplasmic reticulum stress induced GRP78 expression in thyroid carcinoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Guohong Zhao ◽  
Jianqin Kang ◽  
Guanghui Xu ◽  
Jing Wei ◽  
Xiaoguang Wang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Er Stress ◽  
Anaplastic Thyroid Cancer ◽  
Sequencing Data ◽  
Genomic Amplification ◽  
Ecm Remodeling ◽  
Kegg Pathways ◽  
Normal Tissues ◽  
Underlying Mechanisms

Abstract Background Thyroid cancer (TC) is the most common type of endocrine malignancy and its incidence is increasing over years. Conventional surgery, radiotherapy and chemotherapy are difficult to improve the significant effects of it due to aggression and metastasis of poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC), and these are regarded as the most malignant types of TC. Glucose-regulated protein (GRP78) is the key molecule of tumor growth, apoptosis and metastasis. However, the underlying mechanisms of GRP78 in TC still require discussion. This study aimed to explore the role of GRP78 and its potential mechanism in TC. Results GRP78 expression was increased in TC tissues when compared with adjacent normal tissues. Besides, down-regulation of GRP78 significantly inhibited the metastatic and proliferative ability of ATC cells in in vitro studies. In addition, tunicamycin-induced ER stress up-regulated the expression of GRP78, PERK and XBP1 as well as reversed the metastatic ability of GRP78 in ATC cells. Bioinformatics and statistical analysis of gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for RNA-sequencing data with regard to si-GRP78 and si-control showed that GRP78 might regulate the ability of metastasis through extracellular matrix (ECM) remodeling in ATC cells, as well as the expression of ECM components such as COL1A1 and MMP13, which were highly relevant to ATC cells. The analysis of GEPIA database confirmed that high genomic amplification of MMP13 and COL1A1 in TC tissues showed correlation with TNM stage. Further western blotting analysis showed that MMP13 might be the target of GRP78 in ATC cells and ER stress could activate the expression of MMP13 that is suppressed by GRP78 depletion. Conclusions GRP78 acts as an important regulator of metastasis under ER stress. In addition, the function of GRP78 might be mediated by ECM remodeling in ATC cells, implicating it as a therapeutic target in TC.

scholarly journals GRP78 promotes metastasis by regulation of the endoplasmic reticulum stress through remodeling extracellular matrix in thyroid carcinoma

2020 ◽  
Author(s):  
Guohong Zhao ◽  
Jianqin Kang ◽  
Guanghui Xun ◽  
Jing Wei ◽  
Xiaoguang Wang ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Er Stress ◽  
Anaplastic Thyroid Cancer ◽  
Proliferative Potential ◽  
Genomic Amplification ◽  
Ecm Remodeling ◽  
Kegg Pathways ◽  
Normal Tissues

Abstract Background Thyroid cancer(TC)is the most common type of endocrine malignant tumor and the incidence is increasing by years. Conventional surgery, radiotherapy and chemotherapy are difficult to improve significantly effects due to the aggression and metastasis of poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) which are the most malignant type of thyroid cancer. Glucose-regulated protein (GRP78) as the key molecule is related to tumor growth, apoptosis and metastasis. However, the mechanisms responsible for the effects of TC on GRP78 still need to be discussed. Therefore, the purpose of this study was to explore the presence of GRP78 and the potential mechanism of TC. Results GRP78 expression is increased in thyroid carcinoma tissues in comparison with the adjacent normal tissues. Besides, down-regulation of GRP78 significantly inhibited the metastatic and proliferative potential of ATC cells in vitro studies. In addition, tunicomycin (TM)-induced ER stress could up-regulate the expression of GRP78, PERK and XBP1 as well as reverse metastatic ability of GRP78 in TC cells. Bioinformatics and statistical analysis of gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for RNA-seq data from si-GRP78 and si-control showed GRP78 may regulate the ability of metastasis through the ECM remodeling in ATC cells, as well as the expression of ECM components such as COL1A1 and MMP13 were illustrated to be highly relevant to ATC. The analysis of GEPIA database confirmed that high genomic amplification of MMP13 and COL1A1 in TC tissues and were correlated with TNM stage. A further western blot analysis showed MMP13 may be the target of GRP78 in ATC cells and ER stress could activate the expression of MMP13 which was suppressed by depletion of GRP78. Conclusions GRP78 is an important regulator of metastasis under the ER stress. In addition, GRP78’s functions might be mediated by ECM remodeling in ATC cells, which implicates GRP78 as a therapeutic target in thyroid cancer.

Bioinformatics-based Prediction of the mechanism and targets for BushenjieduDecoction in preventing relapse of acute leukemia

2020 ◽  
Author(s):  
Weilong Sun ◽  
Fujun Yang ◽  
Weipeng Shi ◽  
Xia Tao ◽  
Zhiwei Xi ◽  
...  
Keyword(s):  
Bioinformatics Analysis ◽  
Topological Analysis ◽  
Traditional Chinese Medicines ◽  
Potential Mechanism ◽  
Ppi Network ◽  
Chinese Medicines ◽  
Kegg Pathways ◽  
Long Time ◽  
Underlying Mechanisms

Abstract Background: Leukemia is a lethal myeloproliferative disorder, its’ relapse following chemotherapy is the major concern in clinical practice. For a long time, we found that traditional Chinese medicines such as Bushenjiedudecoction (BSJD) have significant effects on delaying relapse. However, the underlying mechanisms are not clear, which limits the clinical application of BSJD decoction. Methods: Therefore, we tried to make some explorations in this study. We isolated mesenchymal stem cells (MSC) after treated them with BSJD for proteomic analysis. And then 109 targets were screened out through analysis of the shared proteins of that affected by BSJD and those related to leukemia. Subsequently, the data were analyzed by GO functions, KEGG pathways, PPI network and topological analysis, and then some nodes were selected for animal experiment. Results: As a result, we demonstrated the effective targets of BSJD on MSC through bioinformatics analysis and explored the potential mechanism of BSJD from its influence on niches.These targets contains Hspb1、Dnmt1、Mmp2、Thbs1、Crebbp、Hmgb1、Acta2、Cdkn1b、Atg7、Tsc2 and Icam1. Afterwards, we confirmed BSJD reduced the gene expression of ICAM-1 through cultured MSC in vitro.Conclusions: We screened the potential targets of BSJD on MSC through proteomics and bioinformatics analysis, and selected some genes for experimental verification. These studies demonstrated the effect of BSJD on MSC. We hope that this research method could provide a new way of systematically studying the effects of traditional Chinese medicine on diseases.

Synergistic anticancer activity of sorafenib, paclitaxel, and radiation therapy on anaplastic thyroid cancer in vitro and in vivo

Head & Neck ◽  
2020 ◽  
Vol 42 (12) ◽  
pp. 3678-3684
Author(s):  
Soo Young Kim ◽  
Seok‐Mo Kim ◽  
Hojin Chang ◽  
Hang‐Seok Chang ◽  
Cheong Soo Park ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Thyroid Cancer ◽  
Anticancer Activity ◽  
Anaplastic Thyroid Cancer

scholarly journals Antitumor Effect of Various Phytochemicals on Diverse Types of Thyroid Cancers

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 125 ◽  
Author(s):  
Hye-Ji Shin ◽  
Kyung-A Hwang ◽  
Kyung-Chul Choi
Keyword(s):  
Thyroid Cancer ◽  
Animal Studies ◽  
Anaplastic Thyroid Cancer ◽  
Thyroid Cancers ◽  
Anticancer Efficacy ◽  
Other Substances ◽  
English Articles ◽  
Thyroid Cancer Cells ◽  
Inhibit Cell Proliferation

Thyroid cancers developed from the tissues of the thyroid gland are classified into papillary (PTC), follicular (FTC), medullary (MTC), and anaplastic thyroid cancer (ATC). Although thyroid cancers have been generally known as mild forms of cancer, undifferentiated MTC and ATC have a more unfavorable prognosis than differentiated PTC and FTC because they are more aggressive and early metastatic. A variety of therapies such as surgery, radiotherapy, and chemotherapy have been currently used to treat thyroid cancer, but they still have limitations including drug resistance or unfavorable side effects. Phytochemicals are plant-derived chemicals having various physiological activities that are expected to be effective in cancer treatment. In this review, anticancer efficacy of phytochemicals, such as resveratrol, genistein, curcumin, and other substances in each type of thyroid cancer was introduced with their chemopreventive mechanisms. English articles related with thyroid cancer and anti-thyroid cancer of phytochemicals were searched from PubMed and Google Scholar. This article mainly focused on in vitro or animal studies on phytochemicals with anti-thyroid cancer activity. These various phytochemicals have been shown to induce apoptosis in all types of thyroid cancer cells, inhibit cell proliferation and invasion, and to be helpful in enhancing the effect of radioiodine therapy that is a typical therapy to thyroid cancer. These results suggest that thyroid cancer can be more effectively treated by the combinations of phytochemicals and the existing therapies or substances.

scholarly journals Deciphering HLA-I motifs across HLA peptidomes improves neo-antigen predictions and identifies allostery regulating HLA specificity

2017 ◽  
Author(s):  
Michal Bassani-Sternberg ◽  
Chloé Chong ◽  
Philippe Guillaume ◽  
Marthe Solleder ◽  
HuiSong Pak ◽  
...  
Keyword(s):  
A Priori ◽  
Human Leukocyte ◽  
Binding Specificity ◽  
Binding Assays ◽  
Sequencing Data ◽  
Protein Structure Analysis ◽  
Binding Motifs ◽  
Leukocyte Antigen ◽  
Underlying Mechanisms

AbstractThe precise identification of Human Leukocyte Antigen class I (HLA-I) binding motifs plays a central role in our ability to understand and predict (neo-)antigen presentation in infectious diseases and cancer. Here, by exploiting co-occurrence of HLA-I alleles across ten newly generated as well as forty public HLA peptidomics datasets comprising more than 115,000 unique peptides, we show that we can rapidly and accurately identify many HLA-I binding motifs and map them to their corresponding alleles without any a priori knowledge of HLA-I binding specificity. Our approach recapitulates and refines known motifs for 43 of the most frequent alleles, uncovers new motifs for 9 alleles that up to now had less than five known ligands and provides a scalable framework to incorporate additional HLA peptidomics studies in the future. The refined motifs improve neo-antigen and cancer testis antigen predictions, indicating that unbiased HLA peptidomics data are ideal for in silico predictions of neo-antigens from tumor exome sequencing data. The new motifs further reveal allosteric modulation of the binding specificity of HLA-I alleles and we unravel the underlying mechanisms by protein structure analysis, mutagenesis and in vitro binding assays.

scholarly journals Downregulation of long non-coding RNA ZXF1 restricts cell survival by targeting miR-634-GRB2 in lung adenocarcinoma

2020 ◽  
Author(s):  
Xubin Ren ◽  
Nie Xu ◽  
Yunting Zhang ◽  
Tao Wang
Keyword(s):  
Lung Adenocarcinoma ◽  
Luciferase Reporter ◽  
Normal Tissues ◽  
Non Coding Rna ◽  
Enhanced Expression ◽  
Rna Immunoprecipitation ◽  
Underlying Mechanisms ◽  
First Time ◽  
Long Non Coding Rna

Increasing evidence demonstrates that long non-coding RNAs (lncRNAs) play important regulatory roles in mediating initiation and progression of lung adenocarcinoma (LA), which is one of the most lethal in humans. A previous study reported that lncRNAZXF1 was dysregulated in LA and enhanced expression of ZXF1 promoted the invasion and metastasis in LA. However, the effect of ZXF1 on LA progression and its underlying mechanisms were not thoroughly investigated. In our in vitro experiments, qRT-PCR revealed that the expression level of ZXF1 in LA tissues and tumor cells were significantly higher than that in adjacent normal tissues and normal cells. Furthermore, bioinformatics analysis, luciferase reporter assay, western blot and RNA immunoprecipitation (RIP) assay showed that ZXF1 could directly interact with miR-634, which targets GRB2. Therefore, we propose that ZXF1 could function as an oncogene partly by sponging miR-634 and therefore regulating GRB2 expression in LA. Overall, this study demonstrated, for the first time, that the lncRNA ZXF1/miR-634/GRB2 axis plays crucial roles in modulating LA progression. Moreover, lncRNA ZXF1 might potentially improve LA prognosis and serve as a therapeutic target for the treatment of LA.

scholarly journals Daphnetin Attenuated Cisplatin-Induced Acute Nephrotoxicity With Enhancing Antitumor Activity of Cisplatin by Upregulating SIRT1/SIRT6-Nrf2 Pathway

2020 ◽  
Vol 11 ◽  
Author(s):  
Xiaoye Fan ◽  
Wei Wei ◽  
Jingbo Huang ◽  
Liping Peng ◽  
Xinxin Ci
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Cell Damage ◽  
Protective Effects ◽  
Normal Tissues ◽  
Nrf2 Signaling Pathway ◽  
Apoptosis Pathways ◽  
Underlying Mechanisms

Cisplatin (CDDP) is a widely used drug for cancer treatment that exhibits major side effects in normal tissues, such as nephrotoxicity in kidneys. The Nrf2 signaling pathway, a regulator of mitochondrial dysfunction, oxidative stress and inflammation, is a potential therapeutic target in CDDP-induced nephrotoxicity. We explored the underlying mechanisms in wild-type (WT) and Nrf2−/− mice on CDDP-induced renal dysfunction in vivo. We found that Nrf2 deficiency aggravated CDDP-induced nephrotoxicity, and Daph treatment significantly ameliorated the renal injury characterized by biochemical markers in WT mice and reduced the CDDP-induced cell damage. In terms of the mechanism, Daph upregulated the SIRT1 and SIRT6 expression in vivo and in vitro. Furthermore, Daph inhibited the expression level of NOX4, whereas it activated Nrf2 translocation and antioxidant enzymes HO-1 and NQO1, and alleviated oxidative stress and mitochondrial dysfunction. Moreover, Daph suppressed CDDP-induced NF-κB and MAPK inflammation pathways, as well as p53 and cleaved caspase-3 apoptosis pathways. Notably, the protective effects of Daph in WT mice were completely abrogated in Nrf2−/− mice. Moreover, Daph enhanced, rather than attenuated, the tumoricidal effect of CDDP.

Abstract P120: Novel in vitro targeted combination therapies for anaplastic thyroid cancer

2021 ◽  
Author(s):  
Muthusamy Kunnimalaiyaan ◽  
Parag Parekh ◽  
Jalyn Golden ◽  
Ying Anderson ◽  
Stephen Lai ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Anaplastic Thyroid Cancer ◽  
Combination Therapies
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