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lncRNA PSORS1C3 is regulated by glucocorticoids and fine-tunes OCT4 expression in non-pluripotent cells

OCT4 is a transcription factor known for its regulatory roles in stemness, tumorigenesis and stress response. Considering its versatile functions, expression of OCT4 is regulated at different levels. PSORS1C3, a long non-coding RNA overlapped with OCT4, has a putative association with immune mediate...

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Autores principales: Mirzadeh Azad, Fatemeh, Malakootian, Mahshid, Mowla, Seyed Javad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557835/
https://www.ncbi.nlm.nih.gov/pubmed/31182783
http://dx.doi.org/10.1038/s41598-019-44827-7
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author Mirzadeh Azad, Fatemeh
Malakootian, Mahshid
Mowla, Seyed Javad
author_facet Mirzadeh Azad, Fatemeh
Malakootian, Mahshid
Mowla, Seyed Javad
author_sort Mirzadeh Azad, Fatemeh
collection PubMed
description OCT4 is a transcription factor known for its regulatory roles in stemness, tumorigenesis and stress response. Considering its versatile functions, expression of OCT4 is regulated at different levels. PSORS1C3, a long non-coding RNA overlapped with OCT4, has a putative association with immune mediated diseases; however, its exact functions remained to be elucidated. Here, we demonstrated that PSORS1C3 is regulated by glucocorticoids (GC), has two endogenously active promoters, promoter 0 and 1, and two sets of transcripts, short and long variants. According to our findings, PSORS1C3 promoters behaved differently during neural differentiation of NT2 cells and glucocorticoid receptor (GR) activation. In both processes the expression pattern of short variants differed from that of long variants and was similar to OCT4 expression. Furthermore, our data revealed that PSORS1C3’s promoter 0 could act as an enhancer for OCT4 in non-pluripotent cells, where its deletion caused a significant decrease in OCT4 expression. Meanwhile, during GR activation promoter 0 functioned as a negative regulator and alleviated transcription induction of OCT4 after GC treatment. Altogether, our work clarified the structure and regulation of PSORS1C3, explained its relation to immune-related disease through GR signaling and introduced it as a novel fine-tuner of OCT4 expression in non-pluripotent cells.
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spelling pubmed-65578352019-06-19 lncRNA PSORS1C3 is regulated by glucocorticoids and fine-tunes OCT4 expression in non-pluripotent cells Mirzadeh Azad, Fatemeh Malakootian, Mahshid Mowla, Seyed Javad Sci Rep Article OCT4 is a transcription factor known for its regulatory roles in stemness, tumorigenesis and stress response. Considering its versatile functions, expression of OCT4 is regulated at different levels. PSORS1C3, a long non-coding RNA overlapped with OCT4, has a putative association with immune mediated diseases; however, its exact functions remained to be elucidated. Here, we demonstrated that PSORS1C3 is regulated by glucocorticoids (GC), has two endogenously active promoters, promoter 0 and 1, and two sets of transcripts, short and long variants. According to our findings, PSORS1C3 promoters behaved differently during neural differentiation of NT2 cells and glucocorticoid receptor (GR) activation. In both processes the expression pattern of short variants differed from that of long variants and was similar to OCT4 expression. Furthermore, our data revealed that PSORS1C3’s promoter 0 could act as an enhancer for OCT4 in non-pluripotent cells, where its deletion caused a significant decrease in OCT4 expression. Meanwhile, during GR activation promoter 0 functioned as a negative regulator and alleviated transcription induction of OCT4 after GC treatment. Altogether, our work clarified the structure and regulation of PSORS1C3, explained its relation to immune-related disease through GR signaling and introduced it as a novel fine-tuner of OCT4 expression in non-pluripotent cells. Nature Publishing Group UK 2019-06-10 /pmc/articles/PMC6557835/ /pubmed/31182783 http://dx.doi.org/10.1038/s41598-019-44827-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Mirzadeh Azad, Fatemeh
Malakootian, Mahshid
Mowla, Seyed Javad
lncRNA PSORS1C3 is regulated by glucocorticoids and fine-tunes OCT4 expression in non-pluripotent cells
title lncRNA PSORS1C3 is regulated by glucocorticoids and fine-tunes OCT4 expression in non-pluripotent cells
title_full lncRNA PSORS1C3 is regulated by glucocorticoids and fine-tunes OCT4 expression in non-pluripotent cells
title_fullStr lncRNA PSORS1C3 is regulated by glucocorticoids and fine-tunes OCT4 expression in non-pluripotent cells
title_full_unstemmed lncRNA PSORS1C3 is regulated by glucocorticoids and fine-tunes OCT4 expression in non-pluripotent cells
title_short lncRNA PSORS1C3 is regulated by glucocorticoids and fine-tunes OCT4 expression in non-pluripotent cells
title_sort lncrna psors1c3 is regulated by glucocorticoids and fine-tunes oct4 expression in non-pluripotent cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557835/
https://www.ncbi.nlm.nih.gov/pubmed/31182783
http://dx.doi.org/10.1038/s41598-019-44827-7
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