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LncRNA MACC1-AS1 sponges multiple miRNAs and RNA-binding protein PTBP1

Long noncoding RNA (lncRNA) represents a class of endogenous RNAs that regulate gene expression in eukaryotes. To date, the function and underlying mechanism of the majority of mammalian lncRNAs remain unknown. Here, we report that MACC1-AS1, a cognate antisense lncRNA of the sixth intron of the MAC...

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Autores principales: Zhang, Xiaona, Zhou, Yanchun, Chen, Shaoying, Li, Wei, Chen, Weibing, Gu, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904680/
https://www.ncbi.nlm.nih.gov/pubmed/31822653
http://dx.doi.org/10.1038/s41389-019-0182-7
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author Zhang, Xiaona
Zhou, Yanchun
Chen, Shaoying
Li, Wei
Chen, Weibing
Gu, Wei
author_facet Zhang, Xiaona
Zhou, Yanchun
Chen, Shaoying
Li, Wei
Chen, Weibing
Gu, Wei
author_sort Zhang, Xiaona
collection PubMed
description Long noncoding RNA (lncRNA) represents a class of endogenous RNAs that regulate gene expression in eukaryotes. To date, the function and underlying mechanism of the majority of mammalian lncRNAs remain unknown. Here, we report that MACC1-AS1, a cognate antisense lncRNA of the sixth intron of the MACC1 gene, functions as a cell growth modulator and enhances breast tumor progress. RNA pulldown and luciferase assays showed that MACC1-AS1 contained binding sites for multiple miRNAs, including well-known tumor suppressors miR-384 and miR-145-3p that repress the expression of pleiotrophin (PTN) and c-Myc mRNAs. Binding of miR-384 and miR-145-3p miRNAs to MACC1-AS1 alters the cell growth phenotype through increased expression of PTN and c-Myc mRNAs. MACC1-AS1 also competitively interacted with PTBP1, an RNA-binding protein, via a conserved pyrimidine rich motif within this lncRNA. Binding of PTBP1to MACC1-AS1 not only stabilized MACC1-AS1 and enhanced the sponge effect of MACC1-AS1 on miRNAs, but also decreased PTBP1 availability for binding to target mRNAs. Our results define a new dimension into how a lncRNA is able to regulate cell growth by sponging multiple miRNAs and an RNA-binding protein.
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spelling pubmed-69046802019-12-11 LncRNA MACC1-AS1 sponges multiple miRNAs and RNA-binding protein PTBP1 Zhang, Xiaona Zhou, Yanchun Chen, Shaoying Li, Wei Chen, Weibing Gu, Wei Oncogenesis Article Long noncoding RNA (lncRNA) represents a class of endogenous RNAs that regulate gene expression in eukaryotes. To date, the function and underlying mechanism of the majority of mammalian lncRNAs remain unknown. Here, we report that MACC1-AS1, a cognate antisense lncRNA of the sixth intron of the MACC1 gene, functions as a cell growth modulator and enhances breast tumor progress. RNA pulldown and luciferase assays showed that MACC1-AS1 contained binding sites for multiple miRNAs, including well-known tumor suppressors miR-384 and miR-145-3p that repress the expression of pleiotrophin (PTN) and c-Myc mRNAs. Binding of miR-384 and miR-145-3p miRNAs to MACC1-AS1 alters the cell growth phenotype through increased expression of PTN and c-Myc mRNAs. MACC1-AS1 also competitively interacted with PTBP1, an RNA-binding protein, via a conserved pyrimidine rich motif within this lncRNA. Binding of PTBP1to MACC1-AS1 not only stabilized MACC1-AS1 and enhanced the sponge effect of MACC1-AS1 on miRNAs, but also decreased PTBP1 availability for binding to target mRNAs. Our results define a new dimension into how a lncRNA is able to regulate cell growth by sponging multiple miRNAs and an RNA-binding protein. Nature Publishing Group UK 2019-12-10 /pmc/articles/PMC6904680/ /pubmed/31822653 http://dx.doi.org/10.1038/s41389-019-0182-7 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
Zhang, Xiaona
Zhou, Yanchun
Chen, Shaoying
Li, Wei
Chen, Weibing
Gu, Wei
LncRNA MACC1-AS1 sponges multiple miRNAs and RNA-binding protein PTBP1
title LncRNA MACC1-AS1 sponges multiple miRNAs and RNA-binding protein PTBP1
title_full LncRNA MACC1-AS1 sponges multiple miRNAs and RNA-binding protein PTBP1
title_fullStr LncRNA MACC1-AS1 sponges multiple miRNAs and RNA-binding protein PTBP1
title_full_unstemmed LncRNA MACC1-AS1 sponges multiple miRNAs and RNA-binding protein PTBP1
title_short LncRNA MACC1-AS1 sponges multiple miRNAs and RNA-binding protein PTBP1
title_sort lncrna macc1-as1 sponges multiple mirnas and rna-binding protein ptbp1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904680/
https://www.ncbi.nlm.nih.gov/pubmed/31822653
http://dx.doi.org/10.1038/s41389-019-0182-7
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