scholarly journals YAP Regulates the Expression ofHoxa1andHoxc13in Mouse and Human Oral and Skin Epithelial Tissues

2015 ◽  
Vol 35 (8) ◽  
pp. 1449-1461 ◽  
Author(s):  
Ming Liu ◽  
Shuangyun Zhao ◽  
Qingjie Lin ◽  
Xiu-Ping Wang
Keyword(s):  
Cell Proliferation ◽  
Expression Profiles ◽  
Tumor Development ◽  
Gene Expression Profiles ◽  
Tooth Germ ◽  
Conditional Knockout ◽  
Hippo Signaling ◽  
Embryonic Mouse ◽  
Downstream Targets ◽  
Epithelial Tissues

Yes-associated protein (YAP) is a Hippo signaling transcriptional coactivator that plays pivotal roles in stem cell proliferation, organ size control, and tumor development. The downstream targets of YAP have been shown to be highly context dependent. In this study, we used the embryonic mouse tooth germ as a tool to search for the downstream targets of YAP in ectoderm-derived tissues.Yapdeficiency in the dental epithelium resulted in a small tooth germ with reduced epithelial cell proliferation. We compared the gene expression profiles of embryonic day 14.5 (E14.5)Yapconditional knockout andYAPtransgenic mouse tooth germs using transcriptome sequencing (RNA-Seq) and further confirmed the differentially expressed genes using real-time PCR andin situhybridization. We found that YAP regulates the expression ofHoxa1andHoxc13in oral and dental epithelial tissues as well as in the epidermis of skin during embryonic and adult stages. Sphere formation assay suggested thatHoxa1andHoxc13are functionally involved in YAP-regulated epithelial progenitor cell proliferation, and chromatin immunoprecipitation (ChIP) assay implies that YAP may regulateHoxa1andHoxc13expression through TEAD transcription factors. These results provide mechanistic insights into abnormal YAP activities in mice and humans.

Spatial Transcriptomics analysis of uterine gene expression in enhancer of Zeste homolog 2 (Ezh2) conditional knockout mice

2021 ◽  
Author(s):  
Ana M Mesa ◽  
Jiude Mao ◽  
Theresa I Medrano ◽  
Nathan J Bivens ◽  
Alexander Jurkevich ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Expression Profiles ◽  
Reproductive Organs ◽  
Conditional Knockout ◽  
Estrogen Signaling ◽  
Uterine Epithelial Cell ◽  
Stromal Tissue

Abstract Histone proteins undergo various modifications that alter chromatin structure, including addition of methyl groups. Enhancer of homolog 2 (EZH2), is a histone methyltransferase that methylates lysine residue 27, and thereby, suppresses gene expression. EZH2 plays integral role in the uterus and other reproductive organs. We have previously shown that conditional deletion of uterine EZH2 results in increased proliferation of luminal and glandular epithelial cells, and RNAseq analyses reveal several uterine transcriptomic changes in Ezh2 conditional (c) knockout (KO) mice that can affect estrogen signaling pathways. To pinpoint the origin of such gene expression changes, we used the recently developed spatial transcriptomics (ST) method with the hypotheses that Ezh2cKO mice would predominantly demonstrate changes in epithelial cells and/or ablation of this gene would disrupt normal epithelial/stromal gene expression patterns. Uteri were collected from ovariectomized adult WT and Ezh2cKO mice and analyzed by ST. Asb4, Cxcl14, Dio2, and Igfbp5 were increased, Sult1d1, Mt3, and Lcn2 were reduced in Ezh2cKO uterine epithelium vs. WT epithelium. For Ezh2cKO uterine stroma, differentially expressed key hub genes included Cald1, Fbln1, Myh11, Acta2, and Tagln. Conditional loss of uterine Ezh2 also appears to shift the balance of gene expression profiles in epithelial vs. stromal tissue toward uterine epithelial cell and gland development and proliferation, consistent with uterine gland hyperplasia in these mice. Current findings provide further insight into how EZH2 may selectively affect uterine epithelial and stromal compartments. Additionally, these transcriptome data might provide the mechanistic understanding and valuable biomarkers for human endometrial disorders with epigenetic underpinnings.

Intratype variants of the E2 protein from human papillomavirus type 18 induce different gene expression profiles associated with apoptosis and cell proliferation

2019 ◽  
Vol 164 (7) ◽  
pp. 1815-1827 ◽  
Author(s):  
Alma Mariana Fuentes-González ◽  
J. Omar Muñoz-Bello ◽  
Joaquín Manzo-Merino ◽  
Adriana Contreras-Paredes ◽  
Abraham Pedroza-Torres ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Human Papillomavirus ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
E2 Protein

scholarly journals Combinatorial targeting of MTHFD2 and PAICS in purine synthesis as a novel therapeutic strategy

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Chantal Hoi Yin Cheung ◽  
Chia-Lang Hsu ◽  
Chao-Yin Tsuei ◽  
Tzu-Ting Kuo ◽  
Chen-Tsung Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Cancer Progression ◽  
Expression Profiles ◽  
Neuroblastoma Cell ◽  
Neuroblastoma Cells ◽  
Gene Expression Profiles ◽  
Migration Ability ◽  
Purine Synthesis ◽  
One Carbon Metabolism

Abstract MYCN-amplified (MNA) neuroblastoma is an aggressive neural crest-derived pediatric cancer. However, MYCN is indispensable for development and transcriptionally regulates extensive network of genes. Integrating anti-MYCN ChIP-seq and gene expression profiles of neuroblastoma patients revealed the metabolic enzymes, MTHFD2 and PAICS, required for one-carbon metabolism and purine biosynthesis were concomitantly upregulated, which were more susceptible to metastatic neuroblastoma. Moreover, we found that MYCN mediated the folate cycle via MTHFD2, which contributed one-carbon unit to enhance purine synthesis, and further regulated nucleotide production by PAICS in response to cancer progression. Dual knockdown of the MYCN-targeted gene pair, MTHFD2 and PAICS, in MNA neuroblastoma cells synergically reduced cell proliferation, colony formation, migration ability, and DNA synthesis. By systematically screening the compound perturbagens, the gene expression levels of MTHFD2 and PAICS were specifically suppressed by anisomycin and apicidin across cell lines, and our co-treatment results also displayed synergistic inhibition of MNA neuroblastoma cell proliferation. Collectively, targeting a combination of MYCN-targeted genes that interrupts the interconnection of metabolic pathways may overcome drug toxicity and improve the efficacy of current therapeutic agents in MNA neuroblastoma.

IgA nephropathy and mesangial cell proliferation: shared global gene expression profiles

Nephrology ◽  
2002 ◽  
Vol 7 ◽  
pp. S106-S113
Author(s):  
Hideto SAKAI ◽  
Naohiro YANO ◽  
Kimberly J FADDEN-PAIVA ◽  
Masayuki ENDOH ◽  
Kiyoshi KUROKAWA ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Iga Nephropathy ◽  
Mesangial Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Mesangial Cell Proliferation

scholarly journals Downregulation of circ-YES1 Suppresses NSCLC Migration and Proliferation Through The miR-142-3p–HMGB1 Axis

2020 ◽  
Author(s):  
Yongbin Chi ◽  
Yan Wang ◽  
Dawei Zhou ◽  
Wanchao Liu ◽  
Ruodong Han ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Tumor Development ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Downstream Targets ◽  
Cell Proliferation And Migration ◽  
Mouse Xenograft Model ◽  
And Migration ◽  
Proliferation And Migration

Abstract Background: Circular RNAs (circRNAs) are a new family of abundant regulatory RNAs with roles in various types of cancer. While the hsa_circ_0046701 (circ-YES1) function in non-small cell lung cancer (NSCLC) is unclear. Methods: Circ-YES1 expression in normal pulmonary epithelial and NSCLC cells was examined. The small interfering RNA for circ-YES1 was prepared, cell proliferation and migration were assessed. Tumorigenesis in nude mice was assayed to validate the role of circ-YES1. Bioinformatics analyses and luciferase reporter assays were utilized to identify downstream targets of circ-YES1. Results: Compared to normal pulmonary epithelial cells, the circ-YES1 expression increased in NSCLC cells, and cell proliferation and migration were suppressed after circ-YES1 knockdown. Both high mobility group protein B1 (HMGB1) and miR-142-3p were found to be downstream targets of circ-YES1, and miR-142-3p inhibition and HMGB1 overexpression reversed the effects of circ-YES1 knockdown on cell proliferation and migration. Similarly, HMGB1 overexpression reversed the miR-142-3p overexpression effects on these two processes. The imaging experiment results revealed that circ-YES1 knockdown impeded tumor development and metastasis in a nude mouse xenograft model. Conclusion: Taken together, our results show that circ-YES1 promotes tumor development through the miR-142-3p–HMGB1 axis and support the development of circ-YES1 as a new therapeutic NSCLC target.

The changes of gene expression profiles in hydatidiform mole and choriocarcinoma with hyperplasia of trophoblasts

2004 ◽  
Vol 14 (5) ◽  
pp. 984-997 ◽  
Author(s):  
J. Q. Cui ◽  
Y. F. Shi ◽  
H. J. Zhou ◽  
J. Q. Li
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Cdna Microarray ◽  
Expression Profiles ◽  
Hydatidiform Mole ◽  
Gene Expression Profiles ◽  
Small Subunit ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Hydatidiform Moles

The purpose of this study is to investigate changes of gene expression profiles in hydatidiform moles (HM) and choriocarcinoma and to explore causes of trophoblastic hyperplasia. Using cDNA microarray, 4096 genes were analyzed in two pairs of the tissues of HM versus normal villi and in two pairs of normal primary culture trophoblasts versus JAR cell line of choriocarcinoma. The expressions of two genes in normal villi and HM, as well as in JAR and JEG-3, were examined with the help of immunohistochemistry, immunoblot, and reverse transcriptase-polymerase chain reaction in order to confirm the findings of cDNA microarray. Twenty-four genes were upregulated and 65 genes were downregulated in all HM. Four hundred thirty-three genes were upregulated and 380 genes were downregulated in JAR. Forty-six genes were upregulated in both HM and choriocarcinoma, whereas 13 genes were downregulated. Genes associated with the inhibition of cell proliferation were significantly downregulated, whereas genes associated with cell proliferation, malignant transformation, metastasis, and drug resistance were upregulated. Thymidine kinase-1 (TK-1) and small subunit ribonucleotide reductase (RRM-2) were overexpressed in HM, JAR, and JEG-3. The expressions of TK-1 and RRM-2 in moles were positively correlated with proliferative index of trophoblasts. Our results suggest that altered expression of genes exist in HM and choriocarcinoma. Trophoblastic hyperplasia may be involved in the overexpression of DNA synthetic enzymes.

scholarly journals Genetic Predisposition to Hepatocarcinogenesis in Inbred and Outbred Mouse Lines Selected for High or Low Inflammatory Response

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Lilian Rego de Carvalho ◽  
Andrea Borrego ◽  
José Ricardo Jensen ◽  
Wafa Hanna Koury Cabrera ◽  
Aline Marques Santos ◽  
...  
Keyword(s):  
Linkage Analysis ◽  
Liver Tumors ◽  
Expression Profiles ◽  
Inbred Mice ◽  
Tumor Development ◽  
Gene Expression Profiles ◽  
Differential Susceptibility ◽  
Snp Markers ◽  
Mouse Strains ◽  
Specific Gene

AIRmax and AIRmin mouse strains phenotypically selected for high and low acute inflammatory responsiveness (AIR) are, respectively, susceptible or resistant to developing hepatocellular carcinoma (HCC) induced by the chemical carcinogens urethane and diethylnitrosamine (DEN). Early production of TNF-α, IL-1β, and IL-6 in the liver after DEN treatment correlated with tumor development in AIRmax mice. Transcriptome analysis of livers from untreated AIRmax and AIRmin mice showed specific gene expression profiles in each line, which might play a role in their differential susceptibility to HCC. Linkage analysis with SNP markers in F2 (AIRmax×AIRmin) intercross mice revealed two quantitative trait loci (QTL) in chromosomes 2 and 9, which are significantly associated with the number and progression of urethane-induced liver tumors. An independent linkage analysis with an intercross population from A/J and C57BL/6J inbred mice mapped regions in chromosomes 1 and 7 associated with the progression of urethane-induced liver tumors, evidencing the heterogeneity of HCC genetic control.

The Impact of Gene Expression Microarrays in the Evaluation of Lung Carcinoma Subtypes and DNA Copy Number

2008 ◽  
Vol 132 (10) ◽  
pp. 1562-1565
Author(s):  
Montserrat Sanchez-Cespedes
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Gene Amplification ◽  
Genetic Background ◽  
Expression Profiles ◽  
Global Analysis ◽  
Tumor Development ◽  
Gene Expression Profiles ◽  
Molecular Alterations ◽  
The Impact

Abstract Context.—The development of targeted therapies creates a need to accurately classify tumors. Among the more pressing needs are the identification of the complete catalog of genes that are altered in cancer and the accurate discrimination of tumors based on their genetic background. Objectives.—To discuss the use of gene expression profiles to recapitulate the pathology and to distinguish the genetic background of non–small cell lung cancer. Also, to comment on using global analysis of gene expression to identify chromosomal regions carrying clusters of highly expressed genes, likely due to gene amplification. Gene amplification at these regions may target the activation of an oncogene critical to tumor development and potentially important in therapy. Data Sources.—Review of relevant, recent literature on molecular alterations and expression analysis in lung cancer. Conclusions.—The complexity of genetic and epigenetic alterations and the cell type of origin confer marked patterns of gene expression to lung tumors, which differentiate different tumor entities.

IgA nephropathy and mesangial cell proliferation: shared global gene expression profiles

Nephrology ◽  
2002 ◽  
Vol 7 ◽  
pp. S106-S113 ◽  
Author(s):  
Hideto Sakai ◽  
Naohiro Yano ◽  
Kimberly J Fadden-Paiva ◽  
Masayuki Endoh ◽  
Kiyoshi Kurokawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Iga Nephropathy ◽  
Mesangial Cell ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Global Gene Expression ◽  
Mesangial Cell Proliferation
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