Oleanolic acid inhibits epithelial–mesenchymal transition of hepatocellular carcinoma by promoting iNOS dimerization
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PROVIDER: PRJNA492476 | ENA |
REPOSITORIES: ENA
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Project description:Oleanolic acid (OA) exhibits extensive pharmacological activities and takes significant anti-tumor effects. Its pharmacological mechanism, however, are still remained to be further clarified. In this study, we demonstrated that OA attenuated the migration and invasion abilities, resulting in the suppression of the EMT process in liver cancer cells, and inhibited the tumor growth of the PLC-bearing mice. We further proved that inducible nitric oxide synthase (iNOS) may be the potential target of OA. We confirmed that OA could promote the dimerization of iNOS, activating it and subsequently increasing the production of nitric oxide (NO). Further experiments indicated that OA promoted the nitration of specific proteins and consequently suppressed their epithelial–mesenchymal transition (EMT)-related biological functions. Furthermore, it has been confirmed that OA enhanced the anti-tumor effects of regorafenib in liver cancer treatment. These results deepened our understanding of the pharmacological mechanism of the antitumor effect OA, and the importance of NOS as a therapeutic target for liver cancer treatment.
2018-09-22 | GSE120311 | GEO
Project description:FXR activation inhibits CAF tumor-promoting features
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Project description:Kaposi’s Sarcoma (KS) is a heterogenous, multifocal vascular malignancy caused by the human herpesvirus 8 (HHV8), also known as Kaposi’s Sarcoma-Associated Herpesvirus (KSHV). Here, we show that KS lesions express iNOS/NOS2 broadly throughout KS lesions, with enrichment in LANA positive spindle cells. The iNOS byproduct 3-nitrotyrosine is also enriched in LANA positive tumor cells and colocalizes with a fraction of LANA-nuclear bodies. We show that iNOS is highly expressed in the L1T3 tumor model of KS. iNOS expression correlated with KSHV lytic cycle gene expression, which was elevated in late-stage tumors (>4 weeks) but to a lesser degree in early stage (1 week) xenografts. Further, we show that L1T3 tumor growth is sensitive to an inhibitor of nitric oxide, L-NMMA. These finding suggest that iNOS is expressed in KSHV infected endothelial-transformed tumor cells in KS, that iNOS expression depends on tumor microenvironment stress conditions, and that iNOS enzymatic activity contributes to KS tumor growth.
2023-07-14 | GSE222527 | GEO
Project description:In order to better understand signaling events following receptor dimerization involving HER2, we have generated an experimental system in which ErbB dimerization can be controlled. We used gene expression microarrays to identify genes and pathways that are differentially activated by HER2 homodimers and HER2 containing heterodimers. MCF10A-HER2-FKBP-HA cells were treated with AP1510, TGFalpha or heregulin for 48 hrs prior to RNA harvest for array analysis.
2011-05-13 | E-GEOD-22288 | biostudies-arrayexpress
Project description:A M. tuberculosis transposon library was used to infect WT and iNOS-/- mice. Surviving mutants were recovered from spleens, genomic DNA was extracted, and labeled probes were synthesized from transposon ends. Probes from each WT mouse were hybridized with probes from a similar iNOS-/- mouse. Two-condition experiment, Growth in WT vs. iNOS-/- mice. Biological replicates: TraSH probe made from 5 wild type and 5 iNOS-/- mice after 3 weeks of infection and from 8 wild type and 8 iNOS-/- mice after 4 weeks of infection. Technical replicates: TraSH probe was synthesized twice from each mouse and dyes were swapped. One array contains probe from one iNOS-/- and one WT mouse. Each biological replicate has two arrays, representing technical replicate dye swaps from one iNOS-/- and one WT mouse.
2009-08-20 | E-GEOD-17706 | biostudies-arrayexpress
Project description:In order to better understand signaling events following receptor dimerization involving HER2, we have generated an experimental system in which ErbB dimerization can be controlled. We used gene expression microarrays to identify genes and pathways that are differentially activated by HER2 homodimers and HER2 containing heterodimers.
2011-05-13 | GSE22288 | GEO
Project description:Metastasis is the major cause of cancer-related death in patients with colorectal cancer. Although inducible nitric oxide synthase (iNOS) is a crucial regulator of cancer development and progression, its roles in epithelial-mesenchymal transition (EMT) and the pathogenesis of metastatic colorectal cancer have not been fully investigated. Primary colorectal cancer and liver metastatic tissue specimens were analyzed showing 90% of liver metastatic colorectal cancer with reduced expressions of iNOS compared with 6% of primary colorectal cancer. The Cancer Genome Atlas database analyses via cBioPortal reveal that mRNA expression of iNOS negatively correlated with selected EMT markers in colorectal cancer in a cancer type-dependent manner. The transcriptomic profiling (RNA sequencing data) indicates that iNOS knockdown in SW480 colorectal cancer cells induced an EMT program with upregulated expression of selected stem-cell markers. iNOS knockdown did not alter E-cadherin mRNA expression but re-localized it from membrane to cytoplasm through iNOS-GATA4-Crb2-E-cadherin pathway. iNOS knockdown induced a change in cell morphology, and promoted cell invasion and migration in vitro, and metastasis in vivo.
2022-07-13 | GSE178862 | GEO
Project description:A M. tuberculosis transposon library was used to infect WT and iNOS-/- mice. Surviving mutants were recovered from spleens, genomic DNA was extracted, and labeled probes were synthesized from transposon ends. Probes from each WT mouse were hybridized with probes from a similar iNOS-/- mouse.
2009-08-20 | GSE17706 | GEO
Project description:Comparison of two Chlamydia-specific CD4 T cells that are dependent on iNOS to terminate Chlamydia replication in epithelial cells to two Chlamydia-specific CD4 T cells that are iNOS-independent: Chlamydia trachomatis urogenital serovars replicate predominately in epithelial cells lining the reproductive tract. This tissue tropism poses a unique challenge for the host immune system and vaccine development. Studies utilizing the Chlamydia muridarum mouse model have shown that CD4 T cells are critical and sufficient to clear primary genital tract infections. In vitro studies have shown that CD4 T cells terminate the infection in epithelial cells by up regulating epithelial iNOS transcription and nitric oxide production via IFN-gamma and T cell-epithelial cell interactions mediated by LFA-1-ICAM-1. This mechanism however is not critical as iNOS-deficient mice clear infections normally, and IFN-gamma deficient mice clear 99.9% of the infection with near normal kinetics. We recently showed that a subset of Chlamydia-specific CD4 T cell clones were able to terminate replication in epithelial cells using a mechanism that was independent of iNOS and IFN-gamma. That mechanism did not require physical lysis of infected cells, but instead required T cell degranulation. In this study we advanced that work using gene expression microarrays to compare CD4 T cell clones that are able to terminate epithelial replication via an iNOS-independent mechanism to iNOS-dependent CD4 T cell clones. Micro array experiments showed that Plac8 was differentially expressed by the T cell clones having the iNOS-independent mechanism. Plac8-deficient mice had significantly delayed clearance of C. muridarum genital tract infections, and that the large majority of Plac8-deficient mice treated with the iNOS-inhibitor N-monomethyl-L-arginine (MLA) were unable to resolve a C. muridarum genital tract infection over 8 weeks. These results demonstrate that there are two independent and redundant T cell mechanisms for clearing C. muridarum genital tract infections; one mechanism dependent on iNOS, the other mechanism dependent on Plac8. While T cells subsets have been defined by cytokine profiles, there are important subdivisions by effector functions, in this case CD4Plac8. Gene expression study using 4 experimental groups with 4 replicates each.
2012-03-14 | E-GEOD-32128 | biostudies-arrayexpress
Project description:Estrogen Receptor β Activation Inhibits Colitis by Promoting the NLRP6-Mediated Autophagy
| PRJNA637511 | ENA