Expression data from AFB1-treated GNMT knockout mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE18218 | GEO | 2009/10/02
SECONDARY ACCESSION(S): PRJNA119643
REPOSITORIES: GEO
Similar Datasets
Project description:We report that liver nodules from 5/8 (62.5%) male and 4/5 (80%) female Gnmt-/- mice were diagnosed as having HCC. Microarray analysis showed that genes involved in the following pathways were deregulated in different stages of tumorigenesis: Methylation, metabolism, signal transduction, cell proliferation, and cell adhesion. This study reveals that GNMT plays an important role in the prevention of hepatotumorigenesis through regulating detoxification pathways. We postulate that GNMT is a stress-responsive protein and its expression may account for the gender difference of the susceptibility to liver cancer. Liver tissues from aflatoxin B1 (AFB1)-treated wild-type or Gnmt knockout mice at 11weeks old were used for RNA extraction and hybridization on Affymetrix microarrays. Total RNA were mixed in equal proportion from 3 mice.
2009-10-02 | E-GEOD-18218 | biostudies-arrayexpress
Project description:We report that 7 of 7 female Gnmt-/- mice developed hepatocellular carcinoma (HCC), the most common form of liver cancer, at the mean age of 16.1 months. In contrast, only one-third (2/6) of male Gnmt-/- mice had HCC, the remaining had either premature death or liver necrosis. Microarray analysis showed that genes involved in the following pathways were deregulated in different stages of tumorigenesis: S-adenosylmethionine (SAM)-dependent methyltransferases, metabolism, signal transduction, cell proliferation, cell adhesion and immune responses. This study reveals that GNMT plays an important role in the prevention of hapatotumorigenesis through regulating DNA methylaiton and oxidative stress signaling pathways. We postulate that GNMT is a stress-responsive protein and its expression may account for the gender difference of the susceptibility to liver cancer. Keywords: Gnmt knockout Liver tissues from wild-type or Gnmt knockout mice at young ages, devoloping dysplasia nodules or HCC were used for RNA extraction and hybridization on Affymetrix microarrays. For 11 weeks old mice, total RNA were mixed in equal proportion from 3 mice.
2008-12-01 | E-GEOD-9809 | biostudies-arrayexpress
Project description:We report that 7 of 7 female Gnmt-/- mice developed hepatocellular carcinoma (HCC), the most common form of liver cancer, at the mean age of 16.1 months. In contrast, only one-third (2/6) of male Gnmt-/- mice had HCC, the remaining had either premature death or liver necrosis. Microarray analysis showed that genes involved in the following pathways were deregulated in different stages of tumorigenesis: S-adenosylmethionine (SAM)-dependent methyltransferases, metabolism, signal transduction, cell proliferation, cell adhesion and immune responses. This study reveals that GNMT plays an important role in the prevention of hapatotumorigenesis through regulating DNA methylaiton and oxidative stress signaling pathways. We postulate that GNMT is a stress-responsive protein and its expression may account for the gender difference of the susceptibility to liver cancer. Keywords: Gnmt knockout
2008-12-01 | GSE9809 | GEO
Project description:Hepatocellular carcinoma (HCC) is the first cause of death in cirrhotic patients. Liver cirrhosis at a high risk of HCC has abnormal S-Adenosylmethionine (SAMe) levels. Catabolism of SAMe is mainly mediated by Glycine N-methyltransferase (GNMT), Lack in GNMT expression leads to epigenetic regulation of critical carcinogenesis pathways and mounting evidence assigns an essential role of GNMT in HCC. Methods: Here we have studied the role of LKB1-AMPK and RAS in the proliferation and transformation of GNMT-deficient HCC. Results. GNMT-deficient HCC was characterized by LKB1-AMPK misconnection, leading to resistance of apoptosis response mediated by a positive regulation of cAMP-PKA-CaMKKβ cascade. Additionally, Ras-mediated hyperactivation of LKB1 contributes to the proliferation of GNMT-deficient HCC in an ERK/p90RSK-dependent manner. The observed LKB1-induced Ras activation, was due to the regulation of RASGRP3 expression. Notably, the human HCC tumors with poorer prognosis showed the lowest levels of GNMT, p-AMPKα(Thr172) and the highest activation of Ras/LKB1/RASGRP3 axis. The present data suggest a correlation between LKB1 and RAS activity in a context of HCC with low GNMT expression, indicating that activation of the RAS/LKB1/RASGRP3 cascade might possess an important prognostic role in human liver cancer. Furthermore, these findings open the possibility to design new therapeutic strategies for the treatment of liver cancer.
2012-07-01 | GSE34838 | GEO
Project description:Hepatocellular carcinoma (HCC) is the first cause of death in cirrhotic patients. Liver cirrhosis at a high risk of HCC has abnormal S-Adenosylmethionine (SAMe) levels. Catabolism of SAMe is mainly mediated by Glycine N-methyltransferase (GNMT), Lack in GNMT expression leads to epigenetic regulation of critical carcinogenesis pathways and mounting evidence assigns an essential role of GNMT in HCC. Methods: Here we have studied the role of LKB1-AMPK and RAS in the proliferation and transformation of GNMT-deficient HCC. Results. GNMT-deficient HCC was characterized by LKB1-AMPK misconnection, leading to resistance of apoptosis response mediated by a positive regulation of cAMP-PKA-CaMKKM-NM-2 cascade. Additionally, Ras-mediated hyperactivation of LKB1 contributes to the proliferation of GNMT-deficient HCC in an ERK/p90RSK-dependent manner. The observed LKB1-induced Ras activation, was due to the regulation of RASGRP3 expression. Notably, the human HCC tumors with poorer prognosis showed the lowest levels of GNMT, p-AMPKM-NM-1(Thr172) and the highest activation of Ras/LKB1/RASGRP3 axis. The present data suggest a correlation between LKB1 and RAS activity in a context of HCC with low GNMT expression, indicating that activation of the RAS/LKB1/RASGRP3 cascade might possess an important prognostic role in human liver cancer. Furthermore, these findings open the possibility to design new therapeutic strategies for the treatment of liver cancer. HCC induced wild-type or Gnmt knockout mice at 3 weeks old were used for RNA extraction and hybridization on Illumina microarrays. The study comprises three groups of samples: OKER cell line(n=3), GNMT-KO mouse hepatocytes (n=3) ,GNMT-WT mouse hepatocytes(n=3)
2012-06-30 | E-GEOD-34838 | biostudies-arrayexpress
Project description:We report that Gnmt-/- mice have abnormal behavior including spontaneous locomotion activity, PPI, TST and FST. Microarray analysis showed that genes expression profiles in male Gnmt -/- mice Keywords: Gnmt knockout
2011-09-01 | GSE23937 | GEO
Project description:We report that Gnmt-/- mice have abnormal behavior including spontaneous locomotion activity, PPI, TST and FST. Microarray analysis showed that genes expression profiles in male Gnmt -/- mice Keywords: Gnmt knockout Cerebral cortex tissues from wild-type or Gnmt knockout mice were used for RNA extraction and hybridization on Affymetrix microarrays. For 4 weeks old mice, total RNA were mixed in equal proportion from 3 mice.
2011-08-31 | E-GEOD-23937 | biostudies-arrayexpress
Project description:Xenograft model formed by OKER cells (GNMT-KO tumor cell line) in nude mice left flank, treated with siLKB1 by IP injection.
2012-10-11 | E-MEXP-3403 | biostudies-arrayexpress
Project description:Background & Aims. Glycine N-methyltransferase (GNMT) is an essential regulator of the total transmethylation flux in the mammalian liver. Distinct DNA methylation patterns are characteristic of liver development, hepatic de-differentiation and liver disease progression, processes in which the levels of GNMT decrease dramatically by mechanisms still poorly understood. Interestingly, putative binding sites for the microRNA miRNA-873-5p were identified in the 3´UTR of GNMT suggesting a potential role for miRNA-873-5p in GNMT regulation. Results. We have identified that the hepatic expression of miRNA-873-5p was increased in a cohort of cirrhotic and liver cancer patients associated with a down-regulation of GNMT levels. Moreover, during liver development, hepatic de-differentiation and fibrosis, the elevation of miRNA-873-5p coincided with the reduction of GNMT expression, indicating that miRNA-873-5p specifically targets the expression of GNMT. Under these circumstances, inhibition of miRNA-873-5p induced GNMT levels and decreased global CpG methylation and transmethylation flux. Indeed, reestablishment of GNMT expression by miRNA-873-5p inhibition reduced hepatocyte de-differentiation, and abolished completely the mortality produced after bile duct ligation as a result of decreased proinflamatory and profibrogenic markers. miRNA-873-5p knockdown-mediated antifibrotic effect was significantly blunted if its effect on GNMT was blocked. Conclusion. Taken together, our studies highlight the role of miRNA-873-5p as a key regulator of GNMT expression, paving the way for new therapeutical approaches in liver de-differentiation and fibrosis.
2018-12-25 | GSE77840 | GEO
Project description:Predisposition to hepatocarcinogenesis is under polygenic control. We analyzed gene expression patterns of dysplastic liver nodules (DN) and hepatocellular carcinoma (HCC) chemically-induced in F344 and BN rats, respectively susceptible and resistant to hepatocarcinogenesis, to evaluate effector mechanisms of predisposition genes, and commonalties between transcription signatures of rat and human liver lesions. Gene expression profiles were determined by microarray analysis and validated by quantitative RT-PCR and Western blot. Cluster analysis revealed two distinctive gene expression patterns, the first of which included normal liver of F344 and BN rats and BN rat nodules, and the second one F344 nodules and HCC of both strains. Expression of 91 and 55 genes of DN and HCC, respectively, showed significant interstrain differences. Considering genes mostly associated with cell proliferation we identified a signature predicting DN evolution to HCC. Notably, expression of oncosuppressors Csmd1, Dmbt, Dusp1, and Gnmt ,in DN, and Bhmt, Dmbt1, Dusp1, Gadd45g, Gnmt, Napsa, Pp2ca, and Ptpn13, in HCC, was higher in BN than F344 rats. Comparative genomics approach, using gene expression data from rat lesions, and human HCC with different prognosis (based on survival length), revealed expression patterns of BN and F344 lesions close to those of human HCCs with better and poorer prognosis, respectively, suggesting that similar molecular events contribute to create a phenotype prone to progression in rats and human lesions. In conclusion, we identified a molecular signature of DN prone to progress to HCC and suggest that oncosuppressor genes are determinants of the genetically transmitted resistance to hepatocarcinogenesis.
2010-10-09 | GSE24600 | GEO