Abstract:
BACKGROUND:Increased expression of RNA polymerase 1 (POL1) molecular pathway was reported to be associated with increased disease activity in patients with multiple sclerosis (MS). However, the operating molecular mechanisms that characterize the pattern of acute MS relapse activity has not been thoroughly studied. OBJECTIVE:To assess POL1 pathway expression during acute MS relapse. METHODS:We studied POL1 pathway associated biomarkers during the first acute optic neuritis attack of MS, and in relapsing-remitting MS patients treated with disease-modifying drugs (DMDs) experiencing an acute MS relapse or a radiological relapse using gene expression microarrays and quantitative RT-PCR. RESULTS:In MS patients (N = 6) during the first acute optic neuritis attack POL1 pathway activation was evident by over-expression of POL1 related network including transcription factor UBTF and downstream components of Assembly of RNA POL1 complex (p=1.92E-03). POL1 related biomarkers RRN3, POLR1D and LRPPRC were over-expressed x1.6 (p = .002), ×1.7 (p = .01) and x2.0 (p = .001) times higher respectively, in MS patients (N = 30) during acute clinical relapse as compared with remission. Similarly, in MS patients (N = 21) that presented with a radiological relapse, we observed significant activation of POL1 related biomarkers including RRN3 (p = .01), POLR1D (p = .002), POLR1E (p = .0001) and LRPPRC (p = .006), as compared with remission, as well as overexpression of a large group of genes encoding ribosomal proteins like RPS6KA3 (p = 7.2E-6), RRP8 (p = .0002) and RPCS9 (p = .0008). CONCLUSIONS:Our findings demonstrated increased POL1 pathway activity in acute MS relapse and suggest that targeted inactivation of POL1 pathway represent a novel strategy for a better treatment of acute MS relapse.
journal_name
Autoimmun Revjournal_title
Autoimmunity reviewsauthors
Achiron A,Zilkha-Falb R,Feldman A,Bovim M,Rozen O,Sarova-Pinhas I,Magalashvili D,Dolev M,Menascu S,Gurevich Mdoi
10.1016/j.autrev.2018.07.006subject
Has Abstractpub_date
2018-12-01 00:00:00pages
1235-1239issue
12eissn
1568-9972issn
1873-0183pii
S1568-9972(18)30242-8journal_volume
17pub_type
杂志文章,评审abstract::Survivin is a protein functionally important for cell division, apoptosis, and possibly, for micro-RNA biogenesis. It is an established marker of malignant cell transformation. In non-malignant conditions, the unique properties of survivin make it indispensable for homeostasis of the immune system. Indeed, it is requi...
journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
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journal_title:Autoimmunity reviews
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journal_title:Autoimmunity reviews
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doi:10.1016/j.autrev.2007.03.008
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
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journal_title:Autoimmunity reviews
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pub_type: 杂志文章,评审
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
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journal_title:Autoimmunity reviews
pub_type: 杂志文章
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journal_title:Autoimmunity reviews
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2014.01.014
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
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更新日期:2013-08-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2005.08.009
更新日期:2006-02-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
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更新日期:2021-02-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2010.07.007
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2012.07.009
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pub_type: 杂志文章
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,meta分析,评审
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journal_title:Autoimmunity reviews
pub_type: 杂志文章
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pub_type: 历史文章,杂志文章,评审
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更新日期:2012-11-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2008.12.005
更新日期:2009-03-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,meta分析,评审
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更新日期:2012-12-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2015.08.005
更新日期:2015-12-01 00:00:00
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pub_type: 杂志文章,评审
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2016.02.006
更新日期:2016-06-01 00:00:00
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journal_title:Autoimmunity reviews
pub_type: 杂志文章,评审
doi:10.1016/j.autrev.2008.07.002
更新日期:2008-10-01 00:00:00
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