Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA178213 | ENA |
REPOSITORIES: ENA
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Project description:Defining the aging-cancer relationship is a challenging task. Mice deficient in Zmpste24, a metalloproteinase mutated in human progeria and involved in nuclear prelamin A maturation, recapitulate many features of aging. However, their short lifespan and cell-intrinsic and -extrinsic alterations restrict the application and interpretation of carcinogenesis protocols. To circumvent these limitations we have generated Zmpste24 mosaic mice. Interestingly, these mice develop normally - revealing cell-extrinsic mechanisms are preeminent in progeria- and display decreased incidence of infiltrating oral carcinomas. Moreover, ZMPSTE24 knock-down reduces human cancer cell invasiveness. Our results disclose the ZMPSTE24-prelamin A system as an example of antagonistic pleiotropy on cancer and aging, support the potential of cell-based and systemic therapies for progeria, and highlight ZMPSTE24 as a new anticancer target. We used siRNAs to silence ZMPSTE24 in different human cancer cell lines (SCC-40, SCC-2, A549 and MDA-MB-231), and compared their RNA expression profiles with those of mock treated cells. Each experimental condition (ZMPSTE24 or Scrambled siRNA) was performed in duplicate. Thus, a total of 16 array hybridizations were performed.
2014-06-01 | E-GEOD-41799 | biostudies-arrayexpress
Project description:Gene expression in human prostate cancer (PCa) cell lines upon HIC1 silencing
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Project description:Defining the aging-cancer relationship is a challenging task. Mice deficient in Zmpste24, a metalloproteinase mutated in human progeria and involved in nuclear prelamin A maturation, recapitulate many features of aging. However, their short lifespan and cell-intrinsic and -extrinsic alterations restrict the application and interpretation of carcinogenesis protocols. To circumvent these limitations we have generated Zmpste24 mosaic mice. Interestingly, these mice develop normally - revealing cell-extrinsic mechanisms are preeminent in progeria- and display decreased incidence of infiltrating oral carcinomas. Moreover, ZMPSTE24 knock-down reduces human cancer cell invasiveness. Our results disclose the ZMPSTE24-prelamin A system as an example of antagonistic pleiotropy on cancer and aging, support the potential of cell-based and systemic therapies for progeria, and highlight ZMPSTE24 as a new anticancer target.
2014-06-01 | GSE41799 | GEO
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Project description:We compared the transcriptomes of isogenic diploid fibroblasts expressing progerin or elevated levels of wild-type prelamin A with that of wild-type fibroblasts. We subsequently used the reversion towards normal of two phenotypes, reduced cell growth and dismorphic nuclei, by treatment with farnesyltransferase inhibitor (FTI) or overexpression of ZMPSTE24, as a filtering strategy to identify genes linked to the onset of these two phenotypes. We carried out microarray analyses of gene expression profiling in isogenic fibroblasts lines to identify the subset of genes whose expression patterns are strongly altered upon expression of progerin or elevated levels of wild-type lamin A. A filtering strategy was then used to identify potential key effectors. We searched for genes whose expression was reverted towards normal by treatment with farnesyl transferase inibitors (FTI) in both cell lines for 48 hours, or by overexpression of ZMPSTE24 in cells with elevated levels of prelamin A, conditions that improve cell proliferation and leads to a significant decrease in nuclear membrane abnormalities.
2012-08-31 | E-GEOD-40404 | biostudies-arrayexpress
Project description:mRNA profiling in gastric cancer cell line AGS upon miR-25-3p silencing
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