scholarly journals A Targeted Bioinformatics Assessment of Adrenocortical Carcinoma Reveals Prognostic Implications of GABA System Gene Expression

2020 ◽  
Vol 21 (22) ◽  
pp. 8485
Author(s):  
Erika L. Knott ◽  
Nancy J. Leidenheimer
Keyword(s):  
Cell Line ◽  
Cancer Progression ◽  
Adrenocortical Carcinoma ◽  
Patient Survival ◽  
Gabab Receptor ◽  
The Cancer Genome Atlas ◽  
Functional Studies ◽  
Gaba Transporters ◽  
Gaba System ◽  
Metabolic Heterogeneity

Adrenocortical carcinoma (ACC) is a rare but deadly cancer for which few treatments exist. Here, we have undertaken a targeted bioinformatics study of The Cancer Genome Atlas (TCGA) ACC dataset focusing on the 30 genes encoding the γ-aminobutyric acid (GABA) system—an under-studied, evolutionarily-conserved system that is an emerging potential player in cancer progression. Our analysis identified a subset of ACC patients whose tumors expressed a distinct GABA system transcriptome. Transcript levels of ABAT (encoding a key GABA shunt enzyme), were upregulated in over 40% of tumors, and this correlated with several favorable clinical outcomes including patient survival; while enrichment and ontology analysis implicated two cancer-related biological pathways involved in metastasis and immune response. The phenotype associated with ABAT upregulation revealed a potential metabolic heterogeneity among ACC tumors associated with enhanced mitochondrial metabolism. Furthermore, many GABAA receptor subunit-encoding transcripts were expressed, including two (GABRB2 and GABRD) prognostic for patient survival. Transcripts encoding GABAB receptor subunits and GABA transporters were also ubiquitously expressed. The GABA system transcriptome of ACC tumors is largely mirrored in the ACC NCI-H295R cell line, suggesting that this cell line may be appropriate for future functional studies investigating the role of the GABA system in ACC cell growth phenotypes and metabolism.

scholarly journals Silencing of lncRNA MIR497HG via CRISPR/Cas13d Induces Bladder Cancer Progression Through Promoting the Crosstalk Between Hippo/Yap and TGF-β/Smad Signaling

2020 ◽  
Vol 7 ◽  
Author(s):  
Changshui Zhuang ◽  
Ying Liu ◽  
Shengqiang Fu ◽  
Chaobo Yuan ◽  
Jingwen Luo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cell Line ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Pathological Process ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion

A subset of long non-coding RNAs (lncRNAs), categorized as miRNA-host gene lncRNAs (lnc-miRHGs), is processed to produce miRNAs and involved in cancer progression. This work aimed to investigate the influences and the molecular mechanisms of lnc-miRHGs MIR497HG in bladder cancer (BCa). The miR-497 and miR-195 were derived from MIR497HG. We identified that lnc-miRHG MIR497HG and two harbored miRNAs, miR-497 and miR-195, were downregulated in BCa by analyzing The Cancer Genome Atlas and our dataset. Silencing of MIR497HG by CRISPR/Cas13d in BCa cell line 5637 promoted cell growth, migration, and invasion in vitro. Conversely, overexpression of MIR497HG suppressed cell progression in BCa cell line T24. MiR-497/miR-195 mimics rescued significantly the oncogenic roles of knockdown of MIR497HG by CRISPR/Cas13d in BCa. Mechanistically, miR-497 and miR-195 co-ordinately suppressed multiple key components in Hippo/Yap and transforming growth factor β signaling and particularly attenuated the interaction between Yap and Smad3. In addition, E2F4 was proven to be critical for silencing MIR497HG transcription in BCa cells. In short, we propose for the first time to reveal the function and mechanisms of MIR497HG in BCa. Blocking the pathological process may be a potential strategy for the treatment of BCa.

scholarly journals Systematic Multiomics Analysis of Alterations in C1QBP mRNA Expression and Relevance for Clinical Outcomes in Cancers

2019 ◽  
Vol 8 (4) ◽  
pp. 513 ◽  
Author(s):  
Subbroto Saha ◽  
Kyung Kim ◽  
S.M. Islam ◽  
Ssang-Goo Cho ◽  
Minchan Gil
Keyword(s):  
Cancer Progression ◽  
Ribosome Biogenesis ◽  
Patient Survival ◽  
Protein A ◽  
The Cancer Genome Atlas ◽  
Therapeutic Modality ◽  
Relative Expression ◽  
Kaplan Meier ◽  
Infection Processes ◽  
The Relationship

C1QBP (Complement Component 1 Q Subcomponent-Binding Protein), a multicompartmental protein, participates in various cellular processes, including mRNA splicing, ribosome biogenesis, protein synthesis in mitochondria, apoptosis, transcriptional regulation, and infection processes of viruses. The correlation of C1QBP expression with patient survival and molecular function of C1QBP in relation to cancer progression has not been comprehensively studied. Therefore, we sought to systematically investigate the expression of C1QBP to evaluate the change of C1QBP expression and the relationship with patient survival and affected pathways in breast, lung, colon, and bladder cancers as well as lymphoma. Relative expression levels of C1QBP were analyzed using the Oncomine, Gene Expression Across Normal and Tumor Tissue (GENT), and The Cancer Genome Atlas (TCGA) databases. Mutations and copy number alterations in C1QBP were also analyzed using cBioPortal, and subsequently, the relationship between C1QBP expression and survival probability of cancer patients was explored using the PrognoScan database and the R2: Kaplan Meier Scanner. Additionally, the relative expression of C1QBP in other cancers, and correlation of C1QBP expression with patient survival were investigated. Gene ontology and pathway analysis of commonly differentially coexpressed genes with C1QBP in breast, lung, colon, and bladder cancers as well as lymphoma revealed the C1QBP-correlated pathways in these cancers. This data-driven study demonstrates the correlation of C1QBP expression with patient survival and identifies possible C1QBP-involved pathways, which may serve as targets of a novel therapeutic modality for various human cancers.

scholarly journals HMGA1-Regulating microRNAs Let-7a and miR-26a are Downregulated in Human Seminomas

2020 ◽  
Vol 21 (8) ◽  
pp. 3014 ◽  
Author(s):  
Marco De Martino ◽  
Francesco Esposito ◽  
Simona Pellecchia ◽  
Ricardo Cortez Cardoso Penha ◽  
Gerardo Botti ◽  
...  
Keyword(s):  
Cell Line ◽  
Critical Role ◽  
Germ Cell Tumors ◽  
Inverse Correlation ◽  
The Cancer Genome Atlas ◽  
Migration And Invasion ◽  
Testicular Germ Cell ◽  
Functional Studies ◽  
Hmga1 Expression ◽  
Cancer Genome Atlas

Background: Recent studies have underlined HMGA protein’s key role in the onset of testicular germ cell tumors, where HMGA1 is differently expressed with respect to the state of differentiation, suggesting its fine regulation as master regulator in testicular tumorigenesis. Several studies have highlighted that the HMGA1 transcript is strictly regulated by a set of inhibitory microRNAs. Thus, the aim of this study is to test whether HMGA1 overexpression in human seminomas may be induced by the deregulation of miR-26a and Let-7a—two HMGA1-targeting microRNAs. Methods: HMGA1 mRNA and Let-7a and miR-26a levels were measured in a seminoma dataset available in the Cancer Genome Atlas database and confirmed in a subset of seminomas by qRT-PCR and western blot. A TCam-2 seminoma cell line was then transfected with Let-7a and miR-26a and tested for proliferation and motility abilities. Results: an inverse correlation was found between the expression of miR-26a and Let-7a and HMGA1 expression levels in seminomas samples, suggesting a critical role of these microRNAs in HMGA1 levels regulation. Accordingly, functional studies showed that miR-26a and Let-7a inhibited the proliferation, migration and invasion capabilities of the human seminoma derived cell line TCam-2. Conclusions: these data strongly support that the upregulation of HMGA1 levels occurring in seminoma is—at least in part—due to the downregulation of HMGA1-targeting microRNAs.

520: Establishment of an Adrenocortical Carcinoma Cell Line (SO-RY), and its Characterization Including Adrenal Cortical Steroidogenesis

2005 ◽  
Vol 173 (4S) ◽  
pp. 141-142
Author(s):  
Yutaka Kamiyama ◽  
Hiroshi Okada ◽  
Koujiro Nishio ◽  
Takashi Yoshii ◽  
Keisuke Saito ◽  
...  
Keyword(s):  
Cell Line ◽  
Adrenocortical Carcinoma ◽  
Carcinoma Cell ◽  
Carcinoma Cell Line

scholarly journals Iron-Bound Lipocalin-2 from Tumor-Associated Macrophages Drives Breast Cancer Progression Independent of Ferroportin

Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 180
Author(s):  
Christina Mertens ◽  
Matthias Schnetz ◽  
Claudia Rehwald ◽  
Stephan Grein ◽  
Eiman Elwakeel ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Progression ◽  
Tumor Cells ◽  
Cancer Progression ◽  
Lung Metastases ◽  
Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Lipocalin 2 ◽  
Tumor Associated Macrophages

Macrophages supply iron to the breast tumor microenvironment by enforced secretion of lipocalin-2 (Lcn-2)-bound iron as well as the increased expression of the iron exporter ferroportin (FPN). We aimed at identifying the contribution of each pathway in supplying iron for the growing tumor, thereby fostering tumor progression. Analyzing the expression profiles of Lcn-2 and FPN using the spontaneous polyoma-middle-T oncogene (PyMT) breast cancer model as well as mining publicly available TCGA (The Cancer Genome Atlas) and GEO Series(GSE) datasets from the Gene Expression Omnibus database (GEO), we found no association between tumor parameters and Lcn-2 or FPN. However, stromal/macrophage-expression of Lcn-2 correlated with tumor onset, lung metastases, and recurrence, whereas FPN did not. While the total iron amount in wildtype and Lcn-2−/− PyMT tumors showed no difference, we observed that tumor-associated macrophages from Lcn-2−/− compared to wildtype tumors stored more iron. In contrast, Lcn-2−/− tumor cells accumulated less iron than their wildtype counterparts, translating into a low migratory and proliferative capacity of Lcn-2−/− tumor cells in a 3D tumor spheroid model in vitro. Our data suggest a pivotal role of Lcn-2 in tumor iron-management, affecting tumor growth. This study underscores the role of iron for tumor progression and the need for a better understanding of iron-targeted therapy approaches.

scholarly journals INFORM: INFrared-based ORganizational Measurements of tumor and its microenvironment to predict patient survival

2021 ◽  
Vol 7 (6) ◽  
pp. eabb8292
Author(s):  
Saumya Tiwari ◽  
Andre Kajdacsy-Balla ◽  
Joshua Whiteley ◽  
Georgina Cheng ◽  
Stephen M. Hewitt ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Progression ◽  
Spatial Organization ◽  
Infrared Imaging ◽  
Patient Survival ◽  
High Definition ◽  
Risk Of Death ◽  
Measurement Framework ◽  
Spatially Varying ◽  
Physical And Chemical

The structure and organization of a tumor and its microenvironment are often associated with cancer outcomes due to spatially varying molecular composition and signaling. A persistent challenge is to use this physical and chemical spatial organization to understand cancer progression. Here, we present a high-definition infrared imaging–based organizational measurement framework (INFORM) that leverages intrinsic chemical contrast of tissue to label unique components of the tumor and its microenvironment. Using objective and automated computational methods, further, we determine organization characteristics important for prediction. We show that the tumor spatial organization assessed with this framework is predictive of overall survival in colon cancer that adds to capability from clinical variables such as stage and grade, approximately doubling the risk of death in high-risk individuals. Our results open an all-digital avenue for measuring and studying the association between tumor spatial organization and disease progression.

scholarly journals Differential Expression of a Panel of Ten CNTN1-Associated Genes during Prostate Cancer Progression and the Predictive Properties of the Panel towards Prostate Cancer Relapse

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 257
Author(s):  
Yan Gu ◽  
Mathilda Jing Chow ◽  
Anil Kapoor ◽  
Xiaozeng Lin ◽  
Wenjuan Mei ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Differential Expression ◽  
Cancer Progression ◽  
Lncap Cell ◽  
Endocrine Resistance ◽  
Gene Panel ◽  
The Cancer Genome Atlas ◽  
Cancer Center ◽  
Poor Overall Survival ◽  
Cell Renal Cell Carcinoma

Contactin 1 (CNTN1) is a new oncogenic protein of prostate cancer (PC); its impact on PC remains incompletely understood. We observed CNTN1 upregulation in LNCaP cell-derived castration-resistant PCs (CRPC) and CNTN1-mediated enhancement of LNCaP cell proliferation. CNTN1 overexpression in LNCaP cells resulted in enrichment of the CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_3 gene set that facilitates endocrine resistance in breast cancer. The leading-edge (LE) genes (n = 10) of this enrichment consist of four genes with limited knowledge on PC and six genes novel to PC. These LE genes display differential expression during PC initiation, metastatic progression, and CRPC development, and they predict PC relapse following curative therapies at hazard ratio (HR) 2.72, 95% confidence interval (CI) 1.96–3.77, and p = 1.77 × 10−9 in The Cancer Genome Atlas (TCGA) PanCancer cohort (n = 492) and HR 2.72, 95% CI 1.84–4.01, and p = 4.99 × 10−7 in Memorial Sloan Kettering Cancer Center (MSKCC) cohort (n = 140). The LE gene panel classifies high-, moderate-, and low-risk of PC relapse in both cohorts. Additionally, the gene panel robustly predicts poor overall survival in clear cell renal cell carcinoma (ccRCC, p = 1.13 × 10−11), consistent with ccRCC and PC both being urogenital cancers. Collectively, we report multiple CNTN1-related genes relevant to PC and their biomarker values in predicting PC relapse.

scholarly journals CSIG-03. RECONCILING TUMOR HETEROGENEITY IN GLIOBLASTOMA USING A PATHWAY-BASED APPROACH

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii28-ii28
Author(s):  
Alvaro Alvarado ◽  
Kaleab Tessema ◽  
Kunal Patel ◽  
Riki Kawaguchi ◽  
Richard Everson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Patient Survival ◽  
Molecular Subtype ◽  
Gene List ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Molecular Architecture ◽  
Survival Pathways ◽  
Cancer Genome Atlas

Abstract Despite efforts to gain a deeper understanding of its molecular architecture, glioblastoma (GBM) remains uniformly fatal. While genome-based molecular subtyping has revealed that GBMs may be parsed into several molecularly distinct categories, this insight has yielded little progress towards extending patient survival. In particular, the great phenotypic heterogeneity of GBM – both inter and intratumorally – has hindered therapeutic efforts. To this end, we interrogated tumor samples using a pathway-based approach to resolve tumoral heterogeneity. Gene set enrichment analysis (GSEA) was applied to gene expression data and used to provide an overview of each sample that can be compared to other samples by generating sample clusters based on overall patterns of enrichment. The Cancer Genome Atlas (TCGA) samples were clustered using the canonical and oncogenic signatures and in both cases the clustering was distinct from the molecular subtype previously reported and clusters were informative of patient survival. We also analyzed single cell RNA sequencing datasets and uniformly found two clusters of cells enriched for cell cycle regulation and survival pathways. We have validated our approach by generating gene lists from common elements found in the top contributing genesets for a particular cluster and testing the top targets in appropriate gliomasphere patient-derived lines. Samples enriched for cell cycle related genesets showed a decrease in sphere formation capacity when E2F1, out top target, was silenced and when treated with fulvestrant and calcitriol, which were identified as potential drugs targeting this genelist. Conversely, no changes were observed in samples not enriched for this gene list. Finally, we interrogated spatial heterogeneity and found higher enrichment of the proliferative signature in contrast enhancing compared with non-enhancing regions. Our studies relate inter- and intratumoral heterogeneity to critical cellular pathways dysregulated in GBM, with the ultimate goal of establishing a pipeline for patient- and tumor-specific precision medicine.

scholarly journals Akt kinase LANCL2 functions as a key driver in EGFR-mutant lung adenocarcinoma tumorigenesis

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Yuqing Lou ◽  
Jianlin Xu ◽  
Yanwei Zhang ◽  
Wei Zhang ◽  
Xueyan Zhang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Cell Line ◽  
Quantitative Polymerase Chain Reaction ◽  
Mutant Cell ◽  
A549 Cells ◽  
The Cancer Genome Atlas ◽  
Akt Kinase ◽  
Egfr Expression

AbstractEpidermal growth factor receptor (EGFR) is a key oncogene in lung adenocarcinoma (LUAD). Resistance to EGFR tyrosine kinase inhibitors is a major obstacle for EGFR-mutant LUAD patients. Our gene chip array, quantitative polymerase chain reaction validation, and shRNA-based high-content screening identified the Akt kinase lanthionine synthetase C-like protein 2 (LANCL2) as a pro-proliferative gene in the EGFR-mutant LUAD cell line PC9. Therefore, we investigated whether LANCL2 plays a role in promoting cell proliferation and drug resistance in EGFR-mutant LUAD. In silico clinical correlation analysis using the Cancer Genome Atlas Lung Adenocarcinoma dataset revealed a positive correlation between LANCL2 and EGFR expression and an inverse relationship between LANCL2 gain-of-function and survival in LUAD patients. The EGFR-mutant LUAD cell lines PC9 and HCC827 displayed higher LANCL2 expression than the non-EGFR-mutant cell line A549. In addition, LANCL2 was downregulated following gefitinib+pemetrexed combination therapy in PC9 cells. LANCL2 knockdown reduced proliferation and enhanced apoptosis in PC9, HCC827, and A549 cells in vitro and suppressed murine PC9 xenograft tumor growth in vivo. Notably, LANCL2 overexpression rescued these effects and promoted gefitinib + pemetrexed resistance in PC9 and HCC827 cells. Pathway analysis and co-immunoprecipitation followed by mass spectrometry of differentially-expressed genes in LANCL2 knockdown cells revealed enrichment of several cancer signaling pathways. In addition, Filamin A and glutathione S-transferase Mu 3 were identified as two novel protein interactors of LANCL2. In conclusion, LANCL2 promotes tumorigenic proliferation, suppresses apoptosis, and promotes gefitinib+pemetrexed resistance in EGFR-mutant LUAD cells. Based on the positive association between LANCL2, EGFR, and downstream Akt signaling, LANCL2 may be a promising new therapeutic target for EGFR-mutant LUAD.

scholarly journals Regulated expression and function of the GABAB receptor in human pancreatic beta cell line and islets

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Latif Rachdi ◽  
Alicia Maugein ◽  
Severine Pechberty ◽  
Mathieu Armanet ◽  
Juliette Hamroune ◽  
...  
Keyword(s):  
Beta Cell ◽  
Cell Line ◽  
Gabab Receptor ◽  
Pancreatic Beta Cell ◽  
Beta Cell Line ◽  
Regulated Expression ◽  
And Function
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