Cell-specific post-transcriptional regulation of γ-synuclein gene by micro-RNAs.

γ-Synuclein is a member of the synucleins family of small proteins, which consists of three members:α, β- and γ-synuclein. γ-Synuclein is abnormally expressed in a high percentage of advanced and metastatic tumors, but not in normal or benign tissues. Furthermore, γ-synuclein expression is strongly...

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Autores principales:	Irina Surgucheva, Sumedha Gunewardena, H Shanker Rao, Andrei Surguchov
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e4a73259943b45b099c47f60135af70c
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spelling	oai:doaj.org-article:e4a73259943b45b099c47f60135af70c2021-11-18T08:55:47ZCell-specific post-transcriptional regulation of γ-synuclein gene by micro-RNAs.1932-620310.1371/journal.pone.0073786https://doaj.org/article/e4a73259943b45b099c47f60135af70c2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24040069/?tool=EBIhttps://doaj.org/toc/1932-6203γ-Synuclein is a member of the synucleins family of small proteins, which consists of three members:α, β- and γ-synuclein. γ-Synuclein is abnormally expressed in a high percentage of advanced and metastatic tumors, but not in normal or benign tissues. Furthermore, γ-synuclein expression is strongly correlated with disease progression, and can stimulate proliferation, induce invasion and metastasis of cancer cells. γ-Synuclein transcription is regulated basically through the binding of AP-1 to specific sequences in intron 1. Here we show that γ-synuclein expression may be also regulated by micro RNAs (miRs) on post-transcriptional level. According to prediction by several methods, the 3'-untranslated region (UTR) of γ-synuclein gene contains targets for miRs. Insertion of γ-synuclein 3'-UTR downstream of the reporter luciferase (LUC) gene causes a 51% reduction of LUC activity after transfection into SKBR3 and Y79 cells, confirming the presence of efficient targets for miRs in this fragment. Expression of miR-4437 and miR-4674 for which putative targets in 3'-UTR were predicted caused a 61.2% and 60.1% reduction of endogenous γ-synuclein expression confirming their role in gene expression regulation. On the other hand, in cells overexpressing γ-synuclein no significant effect of miRs on γ-synuclein expression was found suggesting that miRs exert their regulatory effect only at low or moderate, but not at high level of γ-synuclein expression. Elevated level of γ-synuclein differentially changes the level of several miRs expression, upregulating the level of some miRs and downregulating the level of others. Three miRs upregulated as a result of γ-synuclein overexpression, i.e., miR-885-3p, miR-138 and miR-497 have putative targets in 3'-UTR of the γ-synuclein gene. Some of miRs differentially regulated by γ-synuclein may modulate signaling pathways and cancer related gene expression. This study demonstrates that miRs might provide cell-specific regulation of γ-synuclein expression and set the stage to further evaluate their role in pathophysiological processes.Irina SurguchevaSumedha GunewardenaH Shanker RaoAndrei SurguchovPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e73786 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Irina Surgucheva Sumedha Gunewardena H Shanker Rao Andrei Surguchov Cell-specific post-transcriptional regulation of γ-synuclein gene by micro-RNAs.
description	γ-Synuclein is a member of the synucleins family of small proteins, which consists of three members:α, β- and γ-synuclein. γ-Synuclein is abnormally expressed in a high percentage of advanced and metastatic tumors, but not in normal or benign tissues. Furthermore, γ-synuclein expression is strongly correlated with disease progression, and can stimulate proliferation, induce invasion and metastasis of cancer cells. γ-Synuclein transcription is regulated basically through the binding of AP-1 to specific sequences in intron 1. Here we show that γ-synuclein expression may be also regulated by micro RNAs (miRs) on post-transcriptional level. According to prediction by several methods, the 3'-untranslated region (UTR) of γ-synuclein gene contains targets for miRs. Insertion of γ-synuclein 3'-UTR downstream of the reporter luciferase (LUC) gene causes a 51% reduction of LUC activity after transfection into SKBR3 and Y79 cells, confirming the presence of efficient targets for miRs in this fragment. Expression of miR-4437 and miR-4674 for which putative targets in 3'-UTR were predicted caused a 61.2% and 60.1% reduction of endogenous γ-synuclein expression confirming their role in gene expression regulation. On the other hand, in cells overexpressing γ-synuclein no significant effect of miRs on γ-synuclein expression was found suggesting that miRs exert their regulatory effect only at low or moderate, but not at high level of γ-synuclein expression. Elevated level of γ-synuclein differentially changes the level of several miRs expression, upregulating the level of some miRs and downregulating the level of others. Three miRs upregulated as a result of γ-synuclein overexpression, i.e., miR-885-3p, miR-138 and miR-497 have putative targets in 3'-UTR of the γ-synuclein gene. Some of miRs differentially regulated by γ-synuclein may modulate signaling pathways and cancer related gene expression. This study demonstrates that miRs might provide cell-specific regulation of γ-synuclein expression and set the stage to further evaluate their role in pathophysiological processes.
format	article
author	Irina Surgucheva Sumedha Gunewardena H Shanker Rao Andrei Surguchov
author_facet	Irina Surgucheva Sumedha Gunewardena H Shanker Rao Andrei Surguchov
author_sort	Irina Surgucheva
title	Cell-specific post-transcriptional regulation of γ-synuclein gene by micro-RNAs.
title_short	Cell-specific post-transcriptional regulation of γ-synuclein gene by micro-RNAs.
title_full	Cell-specific post-transcriptional regulation of γ-synuclein gene by micro-RNAs.
title_fullStr	Cell-specific post-transcriptional regulation of γ-synuclein gene by micro-RNAs.
title_full_unstemmed	Cell-specific post-transcriptional regulation of γ-synuclein gene by micro-RNAs.
title_sort	cell-specific post-transcriptional regulation of γ-synuclein gene by micro-rnas.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/e4a73259943b45b099c47f60135af70c
work_keys_str_mv	AT irinasurgucheva cellspecificposttranscriptionalregulationofgsynucleingenebymicrornas AT sumedhagunewardena cellspecificposttranscriptionalregulationofgsynucleingenebymicrornas AT hshankerrao cellspecificposttranscriptionalregulationofgsynucleingenebymicrornas AT andreisurguchov cellspecificposttranscriptionalregulationofgsynucleingenebymicrornas
_version_	1718421173798174720

Cell-specific post-transcriptional regulation of γ-synuclein gene by micro-RNAs.

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