scholarly journals AKR1C1 as a Biomarker for Differentiating the Biological Effects of Combustible from Non-Combustible Tobacco Products

2017 ◽  
Author(s):  
Sangsoon Woo ◽  
Hong Gao ◽  
David Henderson ◽  
Wolfgang Zacharias ◽  
Gang Liu ◽  
...  
Keyword(s):  
Cell Lines ◽  
Smokeless Tobacco ◽  
Artificial Saliva ◽  
Biological Effects ◽  
Differentially Expressed Gene ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Total Particulate Matter ◽  
Tobacco Products ◽  
Potential Biomarker

Smoking has been established as a major risk factor for developing oral squamous cell carcinoma (OSCC), but less attention has been paid to the effects of smokeless tobacco products. Our objective is to identify potential biomarkers to distinguish the biological effects of combustible tobacco products from those of non-combustible using oral cell lines. Normal human gingival epithelial cells (HGEC), non-metastatic (101A) and metastatic (101B) OSCC cell lines were exposed to different tobacco product preparations (TPPs) including cigarette smoke total particulate matter (TPM), whole-smoke conditioned media (WS-CM), smokeless tobacco extract in complete artificial saliva (STE), or nicotine (NIC) alone. We performed microarray-based gene expression profiling and found 3456 probe sets from 101A, 1432 probe sets from 101B, and 2717 probe sets from HGEC to be differentially expressed. Gene Set Enrichment Analysis (GSEA) revealed xenobiotic metabolism and steroid biosynthesis were the top two pathways that were upregulated by combustible but not by non-combustible TPPs. Notably, aldo-keto reductase genes, AKR1C1 and AKR1C2, were the core genes in the top enriched pathways and were statistically upregulated more than 8 fold by combustible TPPs. Our qRT-PCR results statistically support AKR1C1 as a potential biomarker for differentiating the biological effects of combustible from non-combustible tobacco products.

Robust Metabolic Transcriptional Components in 34,494 Patient-Derived Samples and Cell Lines

2021 ◽  
Author(s):  
Vincent Christiaan Leeuwenburgh ◽  
Carlos G. Urzúa-Traslaviña ◽  
Arkajyoti Bhattacharya ◽  
Marthe T.C. Walvoort ◽  
Mathilde Jalving ◽  
...  
Keyword(s):  
Cell Lines ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Metabolic Processes ◽  
Gene Sets ◽  
Transcriptional Changes ◽  
Cancer Tissues ◽  
Tumor Biopsies ◽  
Transcriptional Landscape

Abstract Background: Patient-derived bulk expression profiles of cancers can provide insight into transcriptional changes that underlie reprogrammed metabolism in cancer. These profiles represent the average expression pattern of all heterogeneous tumor and non-tumor cells present in biopsies of tumor lesions. Hence, subtle transcriptional footprints of metabolic processes can be concealed by other biological processes and experimental artifacts. However, consensus Independent Component Analyses (c-ICA) can capture statistically independent transcriptional footprints, of both subtle and more pronounced metabolic processes. Methods: We performed c-ICA with 34,494 bulk expression profiles of patient-derived tumor biopsies, non-cancer tissues, and cell lines. Gene set enrichment analysis with 608 gene sets that describe metabolic processes was performed to identify transcriptional components enriched for metabolic processes (mTCs). The activity of these mTCs were determined in all samples to create a metabolic transcriptional landscape. Results: A set of 555 mTCs were identified of which many were robust across different datasets, platforms, and patient-derived tissues and cell lines. We demonstrate how the metabolic transcriptional landscape defined by the activity of these mTCs in samples can be used to explore associations between the metabolic transcriptome and drug sensitivities, patient outcomes, and the composition of the immune tumor microenvironment. Conclusions: To facilitate the use of our transcriptional metabolic landscape, we have provided access to all data via a web portal ( www.themetaboliclandscapeofcancer.com ). We believe this resource will contribute to the formulation of new hypotheses on how to metabolically engage the tumor or its (immune) microenvironment.

scholarly journals Transcriptomic Analysis of the Differential Nephrotoxicity of Diverse Brominated Flame Retardants in Rat and Human Renal Cells

2021 ◽  
Vol 22 (18) ◽  
pp. 10044
Author(s):  
Lillie Marie A. Barnett ◽  
Naomi E. Kramer ◽  
Amanda N. Buerger ◽  
Deirdre H. Love ◽  
Joseph H. Bisesi ◽  
...  
Keyword(s):  
Cell Lines ◽  
Flame Retardants ◽  
Molecular Mechanisms ◽  
Annexin V ◽  
Enrichment Analysis ◽  
Brominated Flame Retardants ◽  
Human Cells ◽  
Gene Set Enrichment Analysis ◽  
Coagulation Cascade ◽  
Transcriptional Changes

Brominated flame retardants (BFRs) are environmentally persistent, are detected in humans, and some have been banned due to their potential toxicity. BFRs are developmental neurotoxicants and endocrine disruptors; however, few studies have explored their potential nephrotoxicity. We addressed this gap in the literature by determining the toxicity of three different BFRs (tetrabromobisphenol A (TBBPA), hexabromocyclododecane (HBCD), and tetrabromodiphenyl ether (BDE-47)) in rat (NRK 52E) and human (HK-2 and RPTEC) tubular epithelial cells. All compounds induced time- and concentration-dependent toxicity based on decreases in MTT staining and changes in cell and nuclear morphology. The toxicity of BFRs was chemical- and cell-dependent, and human cells were more susceptible to all three BFRs based on IC50s after 48 h exposure. BFRs also had chemical- and cell-dependent effects on apoptosis as measured by increases in annexin V and PI staining. The molecular mechanisms mediating this toxicity were investigated using RNA sequencing. Principal components analysis supported the hypothesis that BFRs induce different transcriptional changes in rat and human cells. Furthermore, BFRs only shared nine differentially expressed genes in rat cells and five in human cells. Gene set enrichment analysis demonstrated chemical- and cell-dependent effects; however, some commonalities were also observed. Namely, gene sets associated with extracellular matrix turnover, the coagulation cascade, and the SNS-related adrenal cortex response were enriched across all cell lines and BFR treatments. Taken together, these data support the hypothesis that BFRs induce differential toxicity in rat and human renal cell lines that is mediated by differential changes in gene expression.

scholarly journals Tumor Expression Profile Analysis Developed and Validated a Prognostic Model Based on Immune-Related Genes in Bladder Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Bingqi Dong ◽  
Jiaming Liang ◽  
Ding Li ◽  
Wenping Song ◽  
Shiming Zhao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Regression Analysis ◽  
Malignant Tumors ◽  
Immune Therapy ◽  
Enrichment Analysis ◽  
R Package ◽  
Gene Set Enrichment Analysis ◽  
Lasso Regression ◽  
Potential Biomarker ◽  
Immune Related Genes

Background: Bladder cancer (BLCA) ranks 10th in incidence among malignant tumors and 6th in incidence among malignant tumors in males. With the application of immune therapy, the overall survival (OS) rate of BLCA patients has greatly improved, but the 5-year survival rate of BLCA patients is still low. Furthermore, not every BLCA patient benefits from immunotherapy, and there are a limited number of biomarkers for predicting the immunotherapy response. Therefore, novel biomarkers for predicting the immunotherapy response and prognosis of BLCA are urgently needed.Methods: The RNA sequencing (RNA-seq) data, clinical data and gene annotation files for The Cancer Genome Atlas (TCGA) BLCA cohort were extracted from the University of California, Santa Cruz (UCSC) Xena Browser. The BLCA datasets GSE31684 and GSE32894 from the Gene Expression Omnibus (GEO) database were extracted for external validation. Immune-related genes were extracted from InnateDB. Significant differentially expressed genes (DEGs) were identified using the R package “limma,” and Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis for the DEGs were performed using R package “clusterProfiler.” Least absolute shrinkage and selection operator (LASSO) regression analysis were used to construct the signature model. The infiltration level of each immune cell type was estimated using the single-sample gene set enrichment analysis (ssGSEA) algorithm. The performance of the model was evaluated with receiver operating characteristic (ROC) curves and calibration curves.Results: In total, 1,040 immune-related DEGs were identified, and eight signature genes were selected to construct a model using LASSO regression analysis. The risk score of BLCA patients based on the signature model was negatively correlated with OS and the immunotherapy response. The ROC curve for OS revealed that the model had good accuracy. The calibration curve showed good agreement between the predictions and actual observations.Conclusions: Herein, we constructed an immune-related eight-gene signature that could be a potential biomarker to predict the immunotherapy response and prognosis of BLCA patients.

scholarly journals Identification of a Novel Epithelial-Mesenchymal Transition Gene Signature Regulated by KEAP1-NRF2 Pathway in Esophageal Carcinoma

2020 ◽  
Author(s):  
Mohamed Elshaer ◽  
Ahmed Hammad ◽  
Xiu Jun Wang ◽  
Xiuwen Tang
Keyword(s):  
Cell Lines ◽  
Epithelial Mesenchymal Transition ◽  
Cancer Cell Line ◽  
Enrichment Analysis ◽  
Gene Signature ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Mesenchymal Transition ◽  
Gene Set ◽  
Over Expression

Abstract BackgroundKEAP1-NRF2 pathway alterations were identified in many cancers including, esophageal cancer (ESCA). Identifying biomarkers that are associated with mutations in this pathway will aid in defining this cancer subset; and hence in supporting precision and personalized medicine. MethodsIn this study, 182 tumor samples from the Cancer Genome Atlas (TCGA)-ESCA RNA-Seq V2 level 3 data were segregated into two groups KEAP1-NRF2-mutated (22) and wild-type (160).The two groups were subjected to differential gene expression analysis, and we performed Gene Set Enrichment Analysis (GSEA) to determine all significantly affected biological pathways. Then, the enriched gene set was integrated with the differentially expressed genes (DEGs) to identify a gene signature regulated by the KEAP1-NRF2 pathway in ESCA. Furthermore, we validated the gene signature using mRNA expression data of ESCA cell lines provided by the Cancer Cell Line Encyclopedia (CCLE). The identified signature was tested in 3 independent ESCA datasets to assess its prognostic value.ResultsWe identified 11 epithelial-mesenchymal transition (EMT) genes regulated by the KEAP1-NRF2 pathway in ESCA patients. Five of the 11 genes showed significant over-expression in KEAP1-NRF2-mutated ESCA cell lines. In addition, the over-expression of these five genes was significantly associated with poor survival in 3 independent ESCA datasets, including the TCGA-ESCA dataset.ConclusionAltogether, we identified a novel EMT 5-gene signature regulated by the KEAP1-NRF2 axis and this signature is strongly associated with metastasis and drug resistance in ESCA. These 5-genes are potential biomarkers and therapeutic targets for ESCA patients in whom the KEAP1-NRF2 pathway is altered.

scholarly journals Transcriptomic Profiling for the Autophagy Pathway in Colorectal Cancer

2020 ◽  
Vol 21 (19) ◽  
pp. 7101
Author(s):  
Justyna Gil ◽  
Paweł Karpiński ◽  
Maria M. Sąsiadek
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Field Cancerization ◽  
Cancer Tissue ◽  
Mrna Levels ◽  
Targeting Therapy ◽  
Autophagy Pathway ◽  
Using Data

The role of autophagy in colorectal cancer (CRC) pathogenesis appears to be crucial. Autophagy acts both as a tumor suppressor, by removing redundant cellular material, and a tumor-promoting factor, by providing access to components necessary for growth, metabolism, and proliferation. To date, little is known about the expression of genes that play a basal role in the autophagy in CRC. In this study, we aimed to compare the expression levels of 46 genes involved in the autophagy pathway between tumor-adjacent and tumor tissue, employing large RNA sequencing (RNA-seq) and microarray datasets. Additionally, we verified our results using data on 38 CRC cell lines. Gene set enrichment analysis revealed a significant deregulation of autophagy-related gene sets in CRC. The unsupervised clustering of tumors using the mRNA levels of autophagy-related genes revealed the existence of two major clusters: microsatellite instability (MSI)-enriched and -depleted. In cluster 1 (MSI-depleted), ATG9B and LAMP1 genes were the most prominently expressed, whereas cluster 2 (MSI-enriched) was characterized by DRAM1 upregulation. CRC cell lines were also clustered according to MSI-enriched/-depleted subgroups. The moderate deregulation of autophagy-related genes in cancer tissue, as compared to adjacent tissue, suggests a prominent field cancerization or early disruption of autophagy. Genes differentiating these clusters are promising candidates for CRC targeting therapy worthy of further investigation.

scholarly journals MicroRNA-550a is associated with muscle system conferring poorer survival for esophageal cancer

2019 ◽  
Vol 39 (5) ◽  
Author(s):  
Housong Hong ◽  
Taisheng Liu ◽  
Huazhen Wu ◽  
Jinye Zhang ◽  
Xiaoshun Shi ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Survival Time ◽  
Therapeutic Target ◽  
Differential Expression Analysis ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Muscle System ◽  
Expression Levels ◽  
Potential Biomarker

Abstract Background Esophageal cancer (ESCA) is one of the most common cancers in the digestive tract. Approximately 300000 people on an average die of ESCA per year worldwide. The determination of key microRNAs for the prognosis of ESCA is of indispensable significance in the clinical treatment. Methods The differentially expressed microRNAs were screened by analyzing The Cancer Genome Atlas (TCGA) database. By using the survival data of the database, we analyzed correlation between patients’ survival time and miR-550a expression levels. Differential expression analysis and gene set enrichment analysis were performed using the targeted data. Results It was found that patients with high miR-550a expression levels had shorter survival time. Data mining and signal pathway enrichment analysis of TCGA database showed that abnormal miR-550a expressions affected the recurrence of tumors by the muscle system regulation. Conclusions Through the proposed investigation, miR-550a is found to be a potential biomarker as well as non-coding therapeutic target for esophagus cancer. These results suggest that miR-550a may serve as a therapeutic target and predictor for ESCA survival.

scholarly journals Circular RNA circ_0003204 inhibits proliferation, migration and tube formation of endothelial cell in atherosclerosis via miR-370-3p/TGFβR2/phosph-SMAD3 axis

2020 ◽  
Vol 27 (1) ◽  
Author(s):  
Shanchao Zhang ◽  
Guixiang Song ◽  
Jing Yuan ◽  
Shan Qiao ◽  
Shan Xu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ectopic Expression ◽  
Enrichment Analysis ◽  
Tube Formation ◽  
Gene Set Enrichment Analysis ◽  
Luciferase Assay ◽  
Circular Rnas ◽  
Human Aorta ◽  
Cerebral Atherosclerosis ◽  
Potential Biomarker

Abstract Background Circular RNAs (circRNAs) represent a class of non-coding RNAs (ncRNAs) which are widely expressed in mammals and tissue-specific, of which some could act as critical regulators in the atherogenesis of cerebrovascular disease. However, the underlying mechanisms by which circRNA regulates the ectopic phenotype of endothelial cells (ECs) in atherosclerosis remain largely elusive. Methods CCK-8, transwell, wound healing and Matrigel assays were used to assess cell viability, migration and tube formation. QRT-qPCR and Immunoblotting were used to examine targeted gene expression in different groups. The binding sites of miR-370-3p (miR-370) with TGFβR2 or hsa_circ_0003204 (circ_0003204) were predicted using a series of bioinformatic tools, and validated using dual luciferase assay and RNA immunoprecipitation (RIP) assay. The localization of circ_0003204 and miR-370 in ECs were investigated by fluorescence in situ hybridization (FISH). Gene function and pathways were enriched through Metascape and gene set enrichment analysis (GSEA). The association of circ_0003204 and miR-370 in extracellular vesicles (EVs) with clinical characteristics of patients were investigated using multiple statistical analysis. Results Circ_0003204, mainly located in the cytoplasm of human aorta endothelial cells (HAECs), was upregulated in the ox-LDL-induced HAECs. Functionally, the ectopic expression of circ_0003204 inhibited proliferation, migration and tube formation of HAECs exposed to ox-LDL. Mechanically, circ_0003204 could promote protein expression of TGFβR2 and its downstream phosph-SMAD3 through sponging miR-370, and miR-370 targeted the 3′ untranslated region (UTR) of TGFβR2. Furthermore, the expression of circ_0003204 in plasma EVs was upregulated in the patients with cerebral atherosclerosis, and represented a potential biomarker for diangnosis and prognosis of cerebrovascular atherogenesis. Conclusions Circ_0003204 could act as a novel stimulator for ectopic endothelial inactivation in atherosclerosis and a potential biomarker for cerebral atherosclerosis.

scholarly journals Comprehensive Analysis of a ceRNA Network Identifies lncR-C3orf35 Associated with Poor Prognosis in Osteosarcoma

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Yi Shi ◽  
Jianhua Ren ◽  
Ze Zhuang ◽  
Wenhui Zhang ◽  
Zhe Wang ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Immune Cell ◽  
Bone Cancer ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
Regulatory Mechanisms ◽  
Messenger Rnas ◽  
Cerna Network ◽  
Potential Biomarker ◽  
Hmgb1 Expression

Osteosarcoma is a highly malignant bone cancer which primarily occurs in children and young adults. Increasing evidence indicates that long noncoding RNAs (lncRNAs), which function as competing endogenous RNAs (ceRNAs) that sponge microRNAs (miRNAs) and messenger RNAs (mRNAs), play a pivotal role in the pathogenesis and progression of cancers. The regulatory mechanisms of lncRNA-mediated ceRNAs in osteosarcoma have not been fully elucidated. In this study, we identified differentially expressed lncRNAs, miRNAs, and mRNAs in osteosarcoma based on RNA microarray profiles in the Gene Expression Omnibus (GEO) database. A ceRNA network was constructed utilizing bioinformatic tools. Kaplan-Meier survival analysis showed that lncR-C3orf35 and HMGB1 were associated with poor prognosis of osteosarcoma patients. Furthermore, results of Gene Set Enrichment Analysis (GSEA) suggested that lncR-C3orf35 may be involved in cellular invasion, the Toll-like receptor signaling pathway, and immune cell infiltration in the tumor microenvironment. Further analysis showed that patients with osteosarcoma metastasis expressed higher levels of lncR-C3orf35 and HMGB1 compared to metastasis-free patients. Moreover, the metastasis-free survival rate of the high lncR-C3orf35/HMGB1 expression group was significantly lower than that of the low expression group. The ESTIMATE algorithm was used to calculate the immune score and stromal scores for each sample. High lncR-C3orf35 and HMGB1 levels were correlated with low immune scores. ImmuCellAI analysis revealed that a low proportion of macrophage infiltration was associated with high lncR-C3orf35 and HMGB1 expression. The differential expression of lncR-C3orf35, miR-142-3p, and HMGB1 was further verified by quantitative real-time PCR. This study indicates that lncR-C3orf35 could be considered as a novel potential biomarker and therapeutic target of osteosarcoma, which may contribute to a better understanding of ceRNA regulatory mechanisms.

Long Non-Coding Sprouty4-Intronic Transcript 1 (SPRY4-IT1) Regulates Cancer Biological Effects and Cisplatin Sensitivity in Cervical Cancer

2019 ◽  
Vol 9 (6) ◽  
pp. 789-796
Author(s):  
Hui Cai ◽  
Hongmei Deng
Keyword(s):  
Cervical Cancer ◽  
Cell Lines ◽  
Cancer Progression ◽  
Biological Effects ◽  
Scratch Test ◽  
Migration And Invasion ◽  
Invasion And Migration ◽  
Potential Biomarker ◽  
Cisplatin Sensitivity ◽  
And Migration

Background: Emerging evidences have revealed that Long noncoding RNAs (LncRNAs) is crucial for cancer progression. Previous studies have elucidated that patients with higher LncRNA SPRY4IT1 was more advanced. This study aims to investigate the biological effects of LncRNA SPRY4-IT1 and preliminary explore the effects of LncRNA SPRY4-IT1 on cisplatin sensitivity. Materials and methods: Quantitative reverse transcriptase PCR was used to validate the expression of SPRY4IT1. Cell migration and invasion were detected by scratch test and Transwell assay. Cell cytometry was performed for cell apoptosis. The expression of proteins was evaluated by immunoblotting. The drug sensitivity was measured by CCK-8. Results: LncRNA SPRY4-IT1 was significantly expressed in cervical cancer cell lines compared to normal cells. Downregulation of LncRNA SPRY4-IT1 in cervical cancer cells suppress the cell viability, cell invasion and migration and promoted apoptosis. In addition, decreases of LncRNA SPRY4-IT1 enhanced the cisplatin sensitivity in cervical cell lines. Conclusion: LncRNA SPRY4-IT1 is a potential biomarker and therapy target for cervical cancer.

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