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Effects on gene expression of nuclear export inhibitor in control and TP53-knockdown cell line of mantle cell lymphoma

ABSTRACT: The TP53 wild-type cell line JVM2, representing mantle cell lymphoma (MCL), was transduced to create control or TP53 knockdown (KD) forms. These were then either left untreated or treated with KPT-185, a selective inhibitor of nuclear export (SINE) by XPO1, for gene expression profiling (GEP). Consistent with the observation that KPT-185 was equally toxic to both forms, the majority of gene expression changes resulting from KPT-185 treatment were similar for both forms, even though TP53 is known to be one of the cargo proteins of XPO1. GEP showed downregulation of genes involved in proliferation, consistent with findings of cell cycle analysis and supported by Western blot results. Quantitative proteomics revealed repression of ribosomal biogenesis to be a major TP53-independent effect of KPT-185.

ORGANISM(S): Homo sapiens

PROVIDER: GSE70479 | GEO | 2015/08/18

SECONDARY ACCESSION(S): PRJNA288798

REPOSITORIES: GEO

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Analysis of gene expression changes in KPT-185-treated HMLE cells transduced to stably overexpress SNAI1

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Identification of Nuclear Export Inhibitor-Based Combination Therapies in Preclinical Models of Triple-Negative Breast Cancer

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Effects of ONC201 on mantle cell lymphoma cell lines

2016-02-20 | E-GEOD-68091 | biostudies-arrayexpress

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Project description:The five-year survival rate remains less than 50% for high-risk neuroblastoma patients, few of them show effective response to current chemotherapy drugs. It is urgent to identify new therapeutic targets and corresponding drugs for high-risk neuroblastoma. Exportin-1(XPO1), also known as chromosomal region maintenance 1 (CRM1), plays important roles in the progress of tumorigenesis. However, the prognostic and therapeutic values of XPO1 in neuroblastoma have not been reported. Here, our results showed that overexpression of XPO1 was significantly associated with poor clinical characteristics and prognosis of neuroblastoma patients. The specific inhibitor of XPO1 suppressed neuroblastoma cell growth both in vitro and in vivo. Specifically, inhibition of XPO1 suppressed neuroblastoma cells proliferation and induced cell apoptosis by FOXO1 and RB1 nuclear accumulation in neuroblastoma through inhibiting PI3K/AKT pathway, and induced G0/G1 phase cell arrest by activating P53 function. Together, XPO1 is a promising prognostic indicator for neuroblastoma and a novel target for antitumor treatment by selective inhibitor verdinexor (KPT-335).

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