scholarly journals Meta-analysis of microarray datasets identify several chromosome segregation-related cancer/testis genes potentially contributing to anaplastic thyroid carcinoma

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5822 ◽  
Author(s):  
Mu Liu ◽  
Yu-lu Qiu ◽  
Tong Jin ◽  
Yin Zhou ◽  
Zhi-yuan Mao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Carcinoma ◽  
Expression Pattern ◽  
Chromosome Segregation ◽  
Drug Targets ◽  
Anaplastic Thyroid Carcinoma ◽  
The Cancer Genome Atlas ◽  
Pathway Enrichment Analysis ◽  
Key Genes ◽  
Cancer Testis

Aim Anaplastic thyroid carcinoma (ATC) is the most lethal thyroid malignancy. Identification of novel drug targets is urgently needed. Materials & Methods We re-analyzed several GEO datasets by systematic retrieval and data merging. Differentially expressed genes (DEGs) were filtered out. We also performed pathway enrichment analysis to interpret the data. We predicted key genes based on protein–protein interaction networks, weighted gene co-expression network analysis and genes’ cancer/testis expression pattern. We also further characterized these genes using data from the Cancer Genome Atlas (TCGA) project and gene ontology annotation. Results Cell cycle-related pathways were significantly enriched in upregulated genes in ATC. We identified TRIP13, DLGAP5, HJURP, CDKN3, NEK2, KIF15, TTK, KIF2C, AURKA and TPX2 as cell cycle-related key genes with cancer/testis expression pattern. We further uncovered that most of these putative key genes were critical components during chromosome segregation. Conclusion We predicted several key genes harboring potential therapeutic value in ATC. Cell cycle-related processes, especially chromosome segregation, may be the key to tumorigenesis and treatment of ATC.

scholarly journals Microarray Data Mining and Preliminary Bioinformatics Analysis of Hepatitis D Virus-Associated Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Zhe Yu ◽  
Xuemei Ma ◽  
Wei Zhang ◽  
Xiujuan Chang ◽  
Linjing An ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
The Cancer Genome Atlas ◽  
Venn Diagram ◽  
Pathway Enrichment Analysis ◽  
Ppi Network ◽  
Hepatitis D ◽  
Increased Risk ◽  
Key Genes

Several studies have demonstrated that chronic hepatitis delta virus (HDV) infection is associated with a worsening of hepatitis B virus (HBV) infection and increased risk of hepatocellular carcinoma (HCC). However, there is limited data on the role of HDV in the oncogenesis of HCC. This study is aimed at assessing the potential mechanisms of HDV-associated hepatocarcinogenesis, especially to screen and identify key genes and pathways possibly involved in the pathogenesis of HCC. We selected three microarray datasets: GSE55092 contains 39 cancer specimens and 81 paracancer specimens from 11 HBV-associated HCC patients, GSE98383 contains 11 cancer specimens and 24 paracancer specimens from 5 HDV-associated HCC patients, and 371 HCC patients with the RNA-sequencing data combined with their clinical data from the Cancer Genome Atlas (TCGA). Afterwards, 948 differentially expressed genes (DEGs) closely related to HDV-associated HCC were obtained using the R package and filtering with a Venn diagram. We then performed gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to determine the biological processes (BP), cellular component (CC), molecular function (MF), and KEGG signaling pathways most enriched for DEGs. Additionally, we performed Weighted Gene Coexpression Network Analysis (WGCNA) and protein-to-protein interaction (PPI) network construction with 948 DEGs, from which one module was identified by WGCNA and three modules were identified by the PPI network. Subsequently, we validated the expression of 52 hub genes from the PPI network with an independent set of HCC dataset stored in the Gene Expression Profiling Interactive Analysis (GEPIA) database. Finally, seven potential key genes were identified by intersecting with key modules from WGCNA, including 3 reported genes, namely, CDCA5, CENPH, and MCM7, and 4 novel genes, namely, CDC6, CDC45, CDCA8, and MCM4, which are associated with nucleoplasm, cell cycle, DNA replication, and mitotic cell cycle. The CDCA8 and stage of HCC were the independent factors associated with overall survival of HDV-associated HCC. All the related findings of these genes can help gain a better understanding of the role of HDV in the underlying mechanism of HCC carcinogenesis.

scholarly journals Integrated Bioinformatics Analysis of Master Regulators in Anaplastic Thyroid Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Zongfu Pan ◽  
Lu Li ◽  
Qilu Fang ◽  
Yangyang Qian ◽  
Yiwen Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Carcinoma ◽  
Signaling Pathway ◽  
Regulatory Network ◽  
Anaplastic Thyroid Carcinoma ◽  
Receptor Interaction ◽  
Ppi Network ◽  
Hub Genes ◽  
Normal Thyroid ◽  
Master Regulators

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive and rapidly lethal tumors. However, limited advances have been made to prolong the survival and to reduce the mortality over the last decades. Therefore, identifying the master regulators underlying ATC progression is desperately needed. In our present study, three datasets including GSE33630, GSE29265, and GSE65144 were retrieved from Gene Expression Omnibus with a total of 32 ATC samples and 78 normal thyroid tissues. A total of 1804 consistently changed differentially expressed genes (DEGs) were identified from three datasets. KEGG pathways enrichment suggested that upregulated DEGs were mainly enriched in ECM-receptor interaction, cell cycle, PI3K-Akt signaling pathway, focal adhesion, and p53 signaling pathway. Furthermore, key gene modules in PPI network were identified by Cytoscape plugin MCODE and they were mainly associated with DNA replication, cell cycle process, collagen fibril organization, and regulation of leukocyte migration. Additionally, TOP2A, CDK1, CCNB1, VEGFA, BIRC5, MAPK1, CCNA2, MAD2L1, CDC20, and BUB1 were identified as hub genes of the PPI network. Interestingly, module analysis showed that 8 out of 10 hub genes participated in Module 1 network and more than 70% genes of Module 2 consisted of collagen family members. Notably, transcription factors (TFs) regulatory network analysis indicated that E2F7, FOXM1, and NFYB were master regulators of Module 1, while CREB3L1 was the master regulator of Module 2. Experimental validation showed that CREB3L1, E2F7, and FOXM1 were significantly upregulated in ATC tissue and cell line when compared with normal thyroid group. In conclusion, the TFs regulatory network provided a more detail molecular mechanism underlying ATC occurrence and progression. TFs including E2F7, FOXM1, CREB3L1, and NFYB were likely to be master regulators of ATC progression, suggesting their potential role as molecular therapeutic targets in ATC treatment.

Butyrate Alters the Expression and Activity of Cell Cycle Components in Anaplastic Thyroid Carcinoma Cells

Thyroid ◽  
2001 ◽  
Vol 11 (1) ◽  
pp. 21-29 ◽  
Author(s):  
Victoria L. Greenberg ◽  
Jennifer M. Williams ◽  
Erwin Boghaert ◽  
Michael Mendenhall ◽  
Kenneth B. Ain ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Carcinoma ◽  
Anaplastic Thyroid Carcinoma ◽  
Carcinoma Cells ◽  
Expression And Activity

scholarly journals Bioinformatics Analysis Identifies Key Genes and Pathways in Acute Myeloid Leukemia Associated with DNMT3A Mutation

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Shuyi Chen ◽  
Yimin Chen ◽  
Jielun Lu ◽  
Danyun Yuan ◽  
Lang He ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Dna Methyltransferase ◽  
Bioinformatics Analysis ◽  
Genetic Alterations ◽  
The Cancer Genome Atlas ◽  
Pathway Enrichment Analysis ◽  
Potential Biomarker ◽  
Key Genes ◽  
Acute Myeloid

Background. DNA methyltransferase 3 alpha (DNMT3A) mutation was one of the most frequent genetic alterations in acute myeloid leukemia (AML), which was associated with poor prognosis and appeared to be a potential biomarker. Herein, we aimed to identify the key genes and pathways involved in adult AML with DNMT3A mutations and to find possible therapeutic targets for improving treatment. Methods. The RNA sequencing datasets of 170 adult AML patients were obtained from The Cancer Genome Atlas (TCGA) database. EdgeR of the R platform was used to identify the differentially expressed genes (DEGs). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Metascape and DAVID. And protein-protein interaction (PPI) network and clustering modules were analyzed with the STRING database and Cytoscape software. Results. Mutated DNMT3A resulted in a shorter overall survival (OS) in AML patients and obviously associated with age, blast percentage in peripheral blood, and FLT3 mutation. A total of 283 DEGs were detected, of which 95 were upregulated and 188 were downregulated. GO term analysis showed that DEGs were significantly enriched in neutrophil degranulation, myeloid cell differentiation, stem cell proliferation, positive regulation of neurological system process, leukocyte migration, and tissue morphogenesis. KEGG pathway enrichment analysis indicated that the pathway of cancer, PI3K-Akt signaling pathway, and transcriptional misregulation in cancer may play a crucial role in DNMT3A mutation AML. Seven hub genes (BMP4, MPO, THBS1, APP, ELANE, HOXA7, and VWF) had a significant prognostic value. Conclusion. Bioinformatics analysis in the present study provided novel targets for early diagnosis and new strategies for treatment for AML with DNMT3A mutation.

scholarly journals HDAC1 and HDAC2 Double Knockout Triggers Cell Apoptosis in Advanced Thyroid Cancer

2019 ◽  
Vol 20 (2) ◽  
pp. 454 ◽  
Author(s):  
Ching-Ling Lin ◽  
Ming-Lin Tsai ◽  
Chun-Yu Lin ◽  
Kai-Wen Hsu ◽  
Wen-Shyang Hsieh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Cancer ◽  
Thyroid Carcinoma ◽  
Histone Acetylation ◽  
Cell Cycle Arrest ◽  
Cell Apoptosis ◽  
Anaplastic Thyroid Carcinoma ◽  
Double Knockout ◽  
Cycle Arrest ◽  
Advanced Thyroid Cancer

Anaplastic thyroid carcinoma (ATC) and squamous thyroid carcinoma (STC) are both rare and advanced thyroid malignancies with a very poor prognosis and an average median survival time of 5 months and less than 20% of affected patients are alive 1 year after diagnosis. The clinical management of both ATC and STC is very similar because they are not particularly responsive to radiotherapy and chemotherapy. This inspired us to explore a novel and effective clinically approved therapy for ATC treatment. Histone deacetylase inhibitor (HDACi) drugs are recently FDA-approved drug for malignancies, especially for blood cell cancers. Therefore, we investigated whether an HDACi drug acts as an effective anticancer drug for advanced thyroid cancers. Cell viability analysis of panobinostat treatment demonstrated a significant IC50 of 0.075 µM on SW579 STC cells. In addition, panobinostat exposure activated histone acetylation and triggered cell death mainly through cell cycle arrest and apoptosis-related protein activation. Using CRISPR/Cas9 to knock out HDAC1 and HDAC2 genes in SW579 cells, we observed that the histone acetylation level and cell cycle arrest were enhanced without any impact on cell growth. Furthermore, HDAC1 and HDAC2 double knockout (KO) cells showed dramatic cell apoptosis activation compared to HDAC1 and HDAC2 individual KO cells. This suggests expressional and biofunctional compensation between HDAC1 and HDAC2 on SW579 cells. This study provides strong evidence that panobinostat can potentially be used in the clinic of advanced thyroid cancer patients.

Diallyl trisulfide induces G2/M cell-cycle arrest and apoptosis in anaplastic thyroid carcinoma 8505C cells

2019 ◽  
Vol 10 (11) ◽  
pp. 7253-7261
Author(s):  
Jiangxia Zheng ◽  
Xian Cheng ◽  
Shichen Xu ◽  
Li Zhang ◽  
Jie Pan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Thyroid Carcinoma ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
Anaplastic Thyroid Carcinoma ◽  
Diallyl Trisulfide ◽  
M Cell ◽  
Cycle Arrest

DATS induces G2/M cell-cycle arrest and apoptosis through ATM-Chk1-Cdc25C signaling pathway in ATC 8505C cells.

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