Investigating the transcriptomics of MCL-1 knockout Nasopharyngeal carcinoma cell lines using next generation microarray technology
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE201440 | GEO | 2024/12/31
REPOSITORIES: GEO
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Project description:Investigating the transcriptomics of MCL-1 knockout Nasopharyngeal carcinoma cell lines using next generation microarray technology
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Project description:Nasopharyngeal carcinoma (NPC) is among a small number of solid tumors that are caused by the Epstein-Barr virus (EBV). Recently, BH3 mimetics, a novel class of drugs that inhibit pro-survival proteins of the BCL-2 family, have demonstrated clinical anti-cancer efficacy in hematological malignancies and are being investigated for use in solid tumors. There is known dysregulation of pro-survival pathways, particularly, the intrinsic apoptotic pathway during EBV infection of B cells suggesting NPC may be driven by the same pathways, and thus sensitive to BH3 inhibition. Using immunohistochemistry, we examined the expression of BCL-2 family of proteins (BCL2, MCL1 and BCLxL) in 174 NPC from patients treated with curative intent as well as five NPC cell lines. We subsequently evaluated the anti-tumor efficacy of three BH3 mimetics (ABT-199, ABT-737 and S63845) in NPC cells alone or in combination with cisplatin, a commonly used cytotoxic agent in NPC treatment. BCL-2 was highly expressed in NPC tumors and cells. Despite this, BCL2 inhibition, or BH3 monotherapy was not effective. However, marked sensitivity was observed with the combination S63845 (targeting MCL-1) and cisplatin in NPC43, which had high expression of MCL-1. This combination resulted in upregulation of pro-apoptotic tBID suggesting a priming role of cisplatin and apoptotic potentiation through MCL-1 inhibition. Flow cytometry studies and RNA sequencing of NPC43 cells treated with the combination of cisplatin with S63845 and untreated cells showed death by apoptosis and upregulation in stress response and DNA damage pathways. Our study suggests that combining BH3 mimetics with cisplatin could be an effective treatment strategy for NPC and warrants further investigation
2024-10-01 | GSE235574 | GEO
Project description:Thermotoga neapolitana Mcl Genome sequencing
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Project description:Comparison of CLL and MCL primary cells obtained from a patient with MCL variant Richter syndrome
2016-07-13 | GSE84286 | GEO
Project description:To analyze the molecular mechanisms by which MCL may induce apoptosis, microarray gene expression profiling of MCL-treated KG1a cells was performed.
2015-12-30 | GSE76384 | GEO
Project description:Patients with conventional mantle cell lymphoma (MCL) show an aggressive clinical behavior. However, cases fulfilling the WHO criteria for MCL, but that remain asymptomatic without treatment, have been reported. In an attempt to understand this heterogeneity, we have compared 17 typical cases of MCL with a homogeneous group of 13 asymptomatic individuals with monoclonal expansion of t(11;14)(q13;q32) cyclin D1-positive B-cells in peripheral blood (MALD1). None of these cases have received treatment (minimum follow-up of 26 months; median, 71 months). Gene expression analysis has shown enrichment of signatures associated to neoplastic behavior and cell proliferation in MCL but not in MALD1. In contrast, MALD1 was highly enriched in gene sets related to immune activation and inflammatory responses. CD38 and CD200 genes were differentially expressed between MCL and MALD1. The combined assessment of both proteins by flow cytometry allowed classifying 85% of MALD1 cases. In summary, we have shown for the first time that MALD1, in contrast to MCL, is characterized by immune activation and driven by inflammatory cues. We have also shown that CD38 and CD200 flow cytometry assessment is useful to discern most cases of MALD1 from MCL in the clinical setting. MALD1 should be identified and segregated from the current MCL category to avoid overdiagnosis and unnecessary treatment.
2013-12-23 | GSE45717 | GEO
Project description:Patients with conventional mantle cell lymphoma (MCL) show an aggressive clinical behavior. However, cases fulfilling the WHO criteria for MCL, but that remain asymptomatic without treatment, have been reported. In an attempt to understand this heterogeneity, we have compared 17 typical cases of MCL with a homogeneous group of 13 asymptomatic individuals with monoclonal expansion of t(11;14)(q13;q32) cyclin D1-positive B-cells in peripheral blood (MALD1). None of these cases have received treatment (minimum follow-up of 26 months; median, 71 months). Gene expression analysis has shown enrichment of signatures associated to neoplastic behavior and cell proliferation in MCL but not in MALD1. In contrast, MALD1 was highly enriched in gene sets related to immune activation and inflammatory responses. CD38 and CD200 genes were differentially expressed between MCL and MALD1. The combined assessment of both proteins by flow cytometry allowed classifying 85% of MALD1 cases. In summary, we have shown for the first time that MALD1, in contrast to MCL, is characterized by immune activation and driven by inflammatory cues. We have also shown that CD38 and CD200 flow cytometry assessment is useful to discern most cases of MALD1 from MCL in the clinical setting. MALD1 should be identified and segregated from the current MCL category to avoid overdiagnosis and unnecessary treatment. 18 samples were analyzed: 5 MALD1, 5 MCL and 8 Healthy Controls
2013-12-23 | E-GEOD-45717 | biostudies-arrayexpress
Project description:Nasopharyngeal carcinoma (NPC) remains a majoy health problem worldwide, specially in Southeast China. In order to find the new candidate genes and molecular markers that are associated with nasopharyngeal carcinoma (NPC), this study focused on the screening NPC relative genes by gene expression profile. Keywords: disease state analysis 23 NPC biopsies and 15 nasopharynx chronic phlogistic biopsies were used to screen NPC relative genes by BioStarH-141s (2004) profile gene chips which contained 14112 points of full length human genes. The tumor samples were labeled with Cy5-dUTP.The nasopharyngeal phlogistic tissues were labeled with Cy3-dUTP. Biostatistics and bioinformatics were also used to analyse the differently expressed genes.
2009-04-21 | E-GEOD-11219 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) have important roles in gene regulation. Dysregulation of miRNAs has been associated with tumorigenesis. Recent studies suggest miR-193b is a tumor suppressor gene. In a previous study, we reported that miR-193b represses cell proliferation and regulates cyclin D1 (CCND1) in melanoma. Now we demonstrate that miR-193b regulates myeloid cell leukemia sequence 1 (Mcl-1) in melanoma cells. miRNA microarray profiling revealed the miR-193b level in malignant melanomas was significantly downregulated compared to benign nevi, while a tissue microarray demonstrated overexpression of Mcl-1 in malignant melanoma. The Mcl-1 expressions were inversely correlated with the miR-193b levels in melanoma tissue samples, suggesting a potential regulatory role of miR-193b. Overexpression of miR-193b repressed Mcl-1 in melanoma cell lines. It is well known that Mcl-1 knockdown confers cell sensitivity to ABT-737, a small molecular inhibitor of Bcl-2, Bcl-XL and Bcl-w. We found miR-193b, through repressing Mcl-1 expression, could also sensitize melanoma cells that were refractory to ABT-737. Furthermore, miR-193b directly regulates Mcl-1 by targeting the 3’ untranslated region (3’UTR) of Mcl-1 mRNA. Interestingly, miR-193b may recognize sequences on the 3’UTR that do not base pair with its seed region. In conclusion, our study suggests the downregulation of miR-193b could be an early event during melanoma progression, and demonstrates miR-193b directly regulates Mcl-1 by targeting both seed and seedless sequences of the 3’ UTR.
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