scholarly journals Master Regulators of Epithelial-Mesenchymal Transition and WNT Signaling Pathways in Juvenile Nasopharyngeal Angiofibromas

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1258
Author(s):  
Naiade Calanca ◽  
Sara Martoreli Silveira Binato ◽  
Sabrina Daniela da Silva ◽  
Helena Paula Brentani ◽  
Luiz Ubirajara Sennes ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Signaling Pathways ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Protein Profile ◽  
Gene Expression Profiles ◽  
Microarray Platform ◽  
Inflammatory Cells ◽  
Nasopharyngeal Angiofibroma ◽  
Mesenchymal Transition

Juvenile nasopharyngeal angiofibroma (JNA) is a rare fibrovascular benign tumor showing an invasive growth pattern and affecting mainly male adolescents. We investigated the role of epithelial–mesenchymal transition (EMT) and WNT signaling pathways in JNA. Gene expression profiles using nine JNA paired with four inferior nasal turbinate samples were interrogated using a customized 2.3K microarray platform containing genes mainly involved in EMT and WNT/PI3K pathways. The expression of selected genes (BCL2, CAV1, CD74, COL4A2, FZD7, ING1, LAMB1, and RAC2) and proteins (BCL2, CAV1, CD74, FZD7, RAF1, WNT5A, and WNT5B) was investigated by RT-qPCR (28 cases) and immunohistochemistry (40 cases), respectively. Among 104 differentially expressed genes, we found a significantly increased expression of COL4A2 and LAMB1 and a decreased expression of BCL2 and RAC2 by RT-qPCR. The immunohistochemistry analysis revealed a low expression of BCL2 and a negative to moderate expression of FZD7 in most samples, while increased CAV1 and RAF1 expression were detected. Moderate to strong CD74 protein expression was observed in endothelial and inflammatory cells. A significant number of JNAs (78%) presented reduced WNT5A and increased WNT5B expression. Overall, the transcript and protein profile indicated the involvement of EMT and WNT pathways in JNA. These candidates are promising druggable targets for treating JNA.

scholarly journals AEBP1 Is One of the Epithelial-Mesenchymal Transition Regulatory Genes in Colon Adenocarcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Dandan Li ◽  
Zhi Liu ◽  
Xiaorong Ding ◽  
Zhensheng Qin
Keyword(s):  
Cancer Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Colon Adenocarcinoma ◽  
The Cancer Genome Atlas ◽  
Mrna Levels ◽  
Mesenchymal Transition ◽  
Tumor Cell Migration ◽  
Promising Target

Epithelial-mesenchymal transition (EMT) is involved in various tumor processes, including tumorigenesis, tumor cell migration and metastasis, tumor stemness, and therapeutic resistance. Therefore, it is important to identify the genes most associated with EMT and develop them as therapeutic targets. In this work, we first analyzed EMT hallmark gene expression profiles among 10,535 pan-cancer samples from The Cancer Genome Atlas (TCGA) and divided them into EMT high and EMT low groups according to the metagene scores. Then, we identified 12 genes that were most associated with high EMT metagene score ( R > 0.9 ) in 329 colon adenocarcinoma (COAD) patients. Among them, only 4 genes (AEBP1, KCNE4, GFPT2, and FAM26E) had statistically significant differences in prognosis ( P < 0.05 ). Next, we selected AEBP1 as a candidate and showed that AEBP1 mRNA levels and EMT biomarkers strongly coexpressed in 329 COAD samples. In addition, AEBP1 was highly expressed and associated with poor clinical outcomes and prognosis in COAD patients. Finally, to explore whether AEBP1-mediated EMT was related to the tumor microenvironment (TME), we examined AEBP1 expression levels at the single-cell levels. Our results showed that AEBP1 levels were extremely high in tumor-associated fibroblasts, which may induce EMT. AEBP1 expression was also positively correlated with the expression of fibroblast biomarkers and also with EMT metascores, suggesting that AEBP1-mediated EMT may be associated with the stimulation of fibroblast activation. Therefore, AEBP1 may be a promising target for EMT inhibition, which reduces cancer metastasis and drug resistance in COAD patients.

scholarly journals A COMPARATIVE ANALAYSIS OF INTER-SITE GENE EXPRESSION HETEROGENICITY OF NORMAL HUMAN BUCCAL MUCOSA WITH NORMAL GINGIVAL MUCOSA

2021 ◽  
Author(s):  
Rooban Thavarajah ◽  
Kannan Ranganathan
Keyword(s):  
Gene Expression ◽  
Buccal Mucosa ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Gene Expression Omnibus ◽  
Genotypic Difference ◽  
Mesenchymal Transition ◽  
Normal Human ◽  
The Difference

BACKGROUND: Description of heterogeneity of gene expression of various human intraoral sites are not adequate. The aim of this study was to explore the difference of gene expression profiles of whole tissue obtained from apparently normal human gingiva and buccal mucosa (HGM, HBM). MATERIALS AND METHODS: Gene sets fulfilling inclusion and exclusion criteria of HGM and HBM in gene Expression Omnibus(GEO) database were identified, segregated, filtered and analysed using the ExAtlas online web tool using pre-determined cut-off. The differentially expressed genes were studied for epithelial keratinization related, housekeeping(HKG), extracellular matrix related(ECMRG) and epithelial-mesenchymal transition related genes(EMTRGs). RESULTS: In all 40 HBM and 64 HGM formed the study group. In all there were 18012 significantly expressed genes. Of this, 1814 were over-expressed and 1862 under-expressed HBM genes as compared to HGM. One in five of all studied genes significantly differed between HBM and HGM. For the keratinization genes, 1 in 6 differed. One of every 5 HKG-proteomics genes differed between HBM and HGM, while this ratio was 1-in 4 for all ECMRGs and EMTRGs. DISCUSSION: This difference in the gene expression between the HBM and HGM could possibly influence a multitude of biological pathways. This result could explain partly the difference in clinicopathological features of oral lesions occurring in HBM and HGM. The innate genotypic difference between the two intra-oral niches could serve as confounding factor in genotypic studies. Hence studies that compare the HBM and HGM should factor-in these findings while evaluating their results.

scholarly journals Gene expression profiling of fast- and slow-growing non-functioning gonadotroph pituitary adenomas

2018 ◽  
Vol 178 (3) ◽  
pp. 295-307 ◽  
Author(s):  
Camilla Maria Falch ◽  
Arvind Y M Sundaram ◽  
Kristin Astrid Øystese ◽  
Kjersti Ringvoll Normann ◽  
Tove Lekva ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tumor Growth ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Growth Potential ◽  
Mesenchymal Transition ◽  
Volume Doubling Time ◽  
Slow Growing

ObjectiveReliable biomarkers associated with aggressiveness of non-functioning gonadotroph adenomas (GAs) are lacking. As the growth of tumor remnants is highly variable, molecular markers for growth potential prediction are necessary. We hypothesized that fast- and slow-growing GAs present different gene expression profiles and reliable biomarkers for tumor growth potential could be identified, focusing on the specific role of epithelial-mesenchymal transition (EMT).Design and methodsEight GAs selected for RNA sequencing were equally divided into fast- and slow-growing group by the tumor volume doubling time (TVDT) median (27.75 months). Data were analyzed by tophat2, cufflinks and cummeRbund pipeline. 40 genes were selected for RT-qPCR validation in 20 GAs based on significance, fold-change and pathway analyses. The effect of silencingMTDH(metadherin) andEMCN(endomucin) onin vitromigration of human adenoma cells was evaluated.Results350 genes were significantly differentially expressed (282 genes upregulated and 68 downregulated in the fast group,P-adjusted <0.05). Among 40 selected genes, 11 showed associations with TVDT (−0.669<R<−0.46,P < 0.05). These werePCDH18, UNC5D, EMCN, MYO1B, GPM6Aand six EMT-related genes (SPAG9, SKIL, MTDH, HOOK1, CNOT6LandPRKACB).MTDH, but notEMCN, demonstrated involvement in cell migration and association with EMT markers.ConclusionsFast- and slow-growing GAs present different gene expression profiles, and genes related to EMT have higher expression in fast-growing tumors. In addition toMTDH, identified as an important contributor to aggressiveness, the other genes might represent markers for tumor growth potential and possible targets for drug therapy.

The diverse genomic landscape of low-risk prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 72-72 ◽  
Author(s):  
Matthew R. Cooperberg ◽  
Nicholas Erho ◽  
June M. Chan ◽  
Felix Yi-Chung Feng ◽  
Janet E. Cowan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Standard Of Care ◽  
Microarray Platform ◽  
Low Risk ◽  
Mesenchymal Transition ◽  
Risk Prostate Cancer ◽  
Low Risk Prostate Cancer

72 Background: Active surveillance (AS) is becoming standard of care for men with low-risk prostate cancer; however a need exists for better tools to assess which men are optimal candidates for AS. In this study we compare genomic expression profiles of AS candidates against higher-risk radical prostatectomy (RP) patients to characterize the genomics of clinically low-risk prostate cancer. Methods: Biopsies from 473 UCSF patients potentially suitable for AS (stage ≤ cT2N0M0, PSA ≤ 10 ng/ml, Gleason 3+3 or low-volume 3+4 ) were profiled using the Affymetrix HuEx microarray to generate RNA expression data. These cases were compared to 2043 RP cases previously profiled on the same microarray platform. Scores for 21 published prognostic signatures were calculated and pathway associated genes were summarized to provide levels of patient risk and pathway activity. Results: Of the 473 AS biopsies profiled, 408 (86%) passed quality control and were used for analysis. Based on the quartiles of average scores for 21 prognostic signature risk models, 49%, 36%, 11%, and 4%, respectively, were classified into the 1st, 2nd, 3rd, or 4th score quartiles. Considering only the clinically low-risk patients at diagnosis, 356 (87%) were low, 45 (11%) were intermediate and 7 (2%) were high risk. Genomic risk was positively associated with cell cycle related pathways (p < 0.001) and negatively associated with apical junction (p < 0.001), epithelial−mesenchymal transition (p < 0.001), and androgen receptor (p < 0.05) pathways. Clustering of patients based on the expression of 36 pathways revealed two biologic groups corresponding to putative basal and luminal subtypes. Compared to higher risk RP patients, the low risk prostate cancer tumors at diagnosis were enriched for basal-like tumors (20% vs 33%, p < 0.001). Conclusions: Although only 2% of low risk AS candidates have high risk genomic characteristics, very substantial genomic heterogeneity exists in this population, and pathway activation overlaps significantly with higher-risk RP patients. These results suggest that even in potential AS candidates, genomic profiling could eventually be used to better guide management.

scholarly journals Modular signature of long non-coding RNA association networks as a prognostic biomarker in lung cancer

2021 ◽  
Vol 14 (S3) ◽  
Author(s):  
Albert Li ◽  
Wen-Hsuan Yu ◽  
Chia-Lang Hsu ◽  
Hsuan-Cheng Huang ◽  
Hsueh-Fen Juan
Keyword(s):  
Lung Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Prognostic Biomarker ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Operating Characteristics ◽  
Mesenchymal Transition ◽  
Cancer Hallmarks ◽  
Non Coding Rna

Abstract Background Increasing amount of long non-coding RNAs (lncRNAs) have been found involving in many biological processes and played salient roles in cancers. However, up until recently, functions of most lncRNAs in lung cancer have not been fully discovered, particularly in the co-regulated lncRNAs. Thus, this study aims to investigate roles of lncRNA modules and uncover a module-based biomarker in lung adenocarcinoma (LUAD). Results We used gene expression profiles from The Cancer Genome Atlas (TCGA) to construct the lncRNA association networks, from which the highly-associated lncRNAs are connected as modules. It was found that the expression of some modules is significantly associated with patient’s survival, including module N1 (HR = 0.62, 95% CI = 0.46–0.84, p = 0.00189); N2 (HR = 0.68, CI = 0.50–0.93, p = 0.00159); N4 (HR = 0.70, CI = 0.52–0.95, p = 0.0205) and P3 (HR = 0.68, CI = 0.50–0.92, p = 0.0123). The lncRNA signature consisting of these four prognosis-related modules, a 4-modular lncRNA signature, is associated with favourable prognosis in TCGA-LUAD (HR = 0.51, CI = 0.37–0.69, p value = 2.00e−05). Afterwards, to assess the performance of the generic modular signature as a prognostic biomarker, we computed the time-dependent area under the receiver operating characteristics (AUC) of this 4-modular lncRNA signature, which showed AUC equals 68.44% on 336th day. In terms of biological functions, these modules are correlated with several cancer hallmarks and pathways, including Myc targets, E2F targets, cell cycle, inflammation/immunity-related pathways, androgen/oestrogen response, KRAS signalling, DNA repair and epithelial-mesenchymal transition (EMT). Conclusion Taken together, we identified four novel LUAD prognosis-related lncRNA modules, and assessed the performance of the 4-modular lncRNA signature being a prognostic biomarker. Functionally speaking, these modules involve in oncogenic hallmarks as well as pathways. The results unveiled the co-regulated lncRNAs in LUAD and may provide a framework for further lncRNA studies in lung cancer.

scholarly journals Identification of Candidate Biomarker ASXL2 and Its Predictive Value in Pancreatic Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Gaoming Wang ◽  
Ludi Yang ◽  
Jinli Gao ◽  
Huiling Mu ◽  
Yanxiang Song ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Predictive Biomarker ◽  
R Package ◽  
Immune Checkpoint Blockade ◽  
Poor Overall Survival ◽  
Aberrant Expression ◽  
Mesenchymal Transition

Pancreatic adenocarcinoma is one of the most lethal diseases with a 5-year survival rate of about 8%. ASXL2 is an epigenetic regulator associated with various tumors including colorectal cancer, breast cancer, and myeloid leukemia. However, the role of ASXL2 in pancreatic cancer remains unclear. This is the first research focusing on the prognostic value of ASXL2 in pancreatic cancer. In this research, we aimed to explore the correlation between ASXL2 and the prognosis, as well as other features in PAAD. We obtained gene expression profiles of PAAD and normal tissues from TCGA, GEO, and Xena databases. TIMER and CIBERSORT algorithms were employed to investigate the effect of ASXL2 on tumor microenvironment. GSEA along with GO and KEGG enrichment analyses were conducted to uncover the biological functions of ASXL2. The response to various chemotherapeutic drugs was estimated by algorithms in R package “pRRophetic”, while the sensitivity to immunotherapy was quantified by TIDE score. We found that ASXL2 was upregulated in the PAAD samples and elevated expression of ASXL2 was linked to poor overall survival. ASXL2 DNA methylation contributed to ASXL2 expression. Functional annotation indicated that ASXL2 was mainly involved in inflammatory response and epithelial mesenchymal transition. Patients with high ASXL2 expression were more likely to benefit from immune checkpoint blockade, gemcitabine, and mitomycin-C. Finally, external datasets and biospecimens were used and the results further validated the aberrant expression of ASXL2 in PAAD samples. In summary, our results highlight that ASXL2 is a potential prognostic and predictive biomarker in pancreatic cancer.

scholarly journals Circular RNA hsa_circ_0000277 sequesters miR-4766-5p to upregulate LAMA1 and promote esophageal carcinoma progression

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Peng Li Zhou ◽  
Zhengyang Wu ◽  
Wenguang Zhang ◽  
Miao Xu ◽  
Jianzhuang Ren ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Epithelial Mesenchymal Transition ◽  
Expression Profiles ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Circular Rnas ◽  
Mesenchymal Transition ◽  
Dismal Prognosis ◽  
Advanced Tumor

AbstractGrowing evidence has indicated that circular RNAs (circRNAs) play a pivotal role as functional RNAs in diverse cancers. However, most circRNAs involved in esophageal squamous cell carcinoma (ESCC) remain undefined, and the underlying molecular mechanisms mediated by circRNAs are largely unclear. Here, we screened human circRNA expression profiles in ESCC tissues and found significantly increased expression of hsa_circ_0000277 (termed circPDE3B) in ESCC tissues and cell lines compared to the normal controls. Moreover, higher circPDE3B expression in patients with ESCC was correlated with advanced tumor-node-metastasis (TNM) stage and dismal prognosis. Functional experiments demonstrated that circPDE3B promoted the tumorigenesis and metastasis of ESCC cells in vitro and in vivo. Mechanistically, bioinformatics analysis, a dual-luciferase reporter assay, and anti-AGO2 RNA immunoprecipitation showed that circPDE3B could act as a competing endogenous RNA (ceRNA) by harboring miR-4766-5p to eliminate the inhibitory effect on the target gene laminin α1 (LAMA1). In addition, LAMA1 was significantly upregulated in ESCC tissues and was positively associated with the aggressive oncogenic phenotype. More importantly, rescue experiments revealed that the oncogenic role of circPDE3B in ESCC is partly dependent on the miR-4766-5p/LAMA1 axis. Furthermore, bioinformatics analysis combined with validation experiments showed that epithelial-mesenchymal transition (EMT) activation was involved in the oncogenic functions of the circPDE3B–miR-4766-5p/LAMA1 axis in ESCC. Taken together, we demonstrate for the first time that the circPDE3B/miR-4766-5p/LAMA1 axis functions as an oncogenic factor in promoting ESCC cell proliferation, migration, and invasion by inducing EMT, implying its potential prognostic and therapeutic significance in ESCC.

scholarly journals Co-Overexpression of TWIST1-CSF1 Is a Common Event in Metastatic Oral Cancer and Drives Biologically Aggressive Phenotype

Cancers ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 153
Author(s):  
Sabrina Daniela da Silva ◽  
Fabio Albuquerque Marchi ◽  
Jie Su ◽  
Long Yang ◽  
Ludmila Valverde ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Inflammatory Cells ◽  
Rank Test ◽  
Mesenchymal Transition ◽  
Genome Wide ◽  
A Genome ◽  
Enhanced Expression ◽  
Advanced Stages

Invasive oral squamous cell carcinoma (OSCC) is often ulcerated and heavily infiltrated by pro-inflammatory cells. We conducted a genome-wide profiling of tissues from OSCC patients (early versus advanced stages) with 10 years follow-up. Co-amplification and co-overexpression of TWIST1, a transcriptional activator of epithelial-mesenchymal-transition (EMT), and colony-stimulating factor-1 (CSF1), a major chemotactic agent for tumor-associated macrophages (TAMs), were observed in metastatic OSCC cases. The overexpression of these markers strongly predicted poor patient survival (log-rank test, p = 0.0035 and p = 0.0219). Protein analysis confirmed the enhanced expression of TWIST1 and CSF1 in metastatic tissues. In preclinical models using OSCC cell lines, macrophages, and an in vivo matrigel plug assay, we demonstrated that TWIST1 gene overexpression induces the activation of CSF1 while TWIST1 gene silencing down-regulates CSF1 preventing OSCC invasion. Furthermore, excessive macrophage activation and polarization was observed in co-culture system involving OSCC cells overexpressing TWIST1. In summary, this study provides insight into the cooperation between TWIST1 transcription factor and CSF1 to promote OSCC invasiveness and opens up the potential therapeutic utility of currently developed antibodies and small molecules targeting cancer-associated macrophages.

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