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Long noncoding RNA HOXA-AS2 represses P21 and KLF2 expression transcription by binding with EZH2, LSD1 in colorectal cancer

Long noncoding RNAs (lncRNAs) have received increased attention as a new class of functional regulators involved in human carcinogenesis. HOXA cluster antisense RNA 2 (HOXA-AS2) is a 1048-bp lncRNA located between the HOXA3 and HOXA4 genes in the HOXA cluster that regulates gene expression at a tran...

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Autores principales: Ding, J, Xie, M, Lian, Y, Zhu, Y, Peng, P, Wang, J, Wang, L, Wang, K
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294247/
https://www.ncbi.nlm.nih.gov/pubmed/28112720
http://dx.doi.org/10.1038/oncsis.2016.84
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author Ding, J
Xie, M
Lian, Y
Zhu, Y
Peng, P
Wang, J
Wang, L
Wang, K
author_facet Ding, J
Xie, M
Lian, Y
Zhu, Y
Peng, P
Wang, J
Wang, L
Wang, K
author_sort Ding, J
collection PubMed
description Long noncoding RNAs (lncRNAs) have received increased attention as a new class of functional regulators involved in human carcinogenesis. HOXA cluster antisense RNA 2 (HOXA-AS2) is a 1048-bp lncRNA located between the HOXA3 and HOXA4 genes in the HOXA cluster that regulates gene expression at a transcription level. HOXA-AS2 is previously found to be overexpressed in gastric cancer (GC) and promotes GC cells proliferation. However, its potential role and molecular mechanism in colorectal cancer (CRC) are not known. Here, we identified that HOXA-AS2 is significantly upregulated in CRC tissue. In addition, increased HOXA-AS2 expression is associated with a larger tumor size and an advanced pathological stage in CRC patients. HOXA-AS2 knockdown significantly suppressed proliferation by blocking the G1/S transition and caused apoptosis of CRC cells in vitro and in vivo. The mechanistic investigations showed that HOXA-AS2 could interact with EZH2 (enhancer of zeste homolog 2), LSD1 (lysine specific demethylase 1) and recruit them to p21 (CDKN1A), KLF2 promoter regions to repress their transcription. Furthermore, the rescue experiments demonstrated that HOXA-AS2 oncogenic function is partly through regulating p21. In conclusion, our data suggest that HOXA-AS2 may function as an oncogene by modulating the multiple genes expression involved in CRC proliferation, and also provides a potential target for CRC therapy.
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spelling pubmed-52942472017-02-14 Long noncoding RNA HOXA-AS2 represses P21 and KLF2 expression transcription by binding with EZH2, LSD1 in colorectal cancer Ding, J Xie, M Lian, Y Zhu, Y Peng, P Wang, J Wang, L Wang, K Oncogenesis Original Article Long noncoding RNAs (lncRNAs) have received increased attention as a new class of functional regulators involved in human carcinogenesis. HOXA cluster antisense RNA 2 (HOXA-AS2) is a 1048-bp lncRNA located between the HOXA3 and HOXA4 genes in the HOXA cluster that regulates gene expression at a transcription level. HOXA-AS2 is previously found to be overexpressed in gastric cancer (GC) and promotes GC cells proliferation. However, its potential role and molecular mechanism in colorectal cancer (CRC) are not known. Here, we identified that HOXA-AS2 is significantly upregulated in CRC tissue. In addition, increased HOXA-AS2 expression is associated with a larger tumor size and an advanced pathological stage in CRC patients. HOXA-AS2 knockdown significantly suppressed proliferation by blocking the G1/S transition and caused apoptosis of CRC cells in vitro and in vivo. The mechanistic investigations showed that HOXA-AS2 could interact with EZH2 (enhancer of zeste homolog 2), LSD1 (lysine specific demethylase 1) and recruit them to p21 (CDKN1A), KLF2 promoter regions to repress their transcription. Furthermore, the rescue experiments demonstrated that HOXA-AS2 oncogenic function is partly through regulating p21. In conclusion, our data suggest that HOXA-AS2 may function as an oncogene by modulating the multiple genes expression involved in CRC proliferation, and also provides a potential target for CRC therapy. Nature Publishing Group 2017-01 2017-01-23 /pmc/articles/PMC5294247/ /pubmed/28112720 http://dx.doi.org/10.1038/oncsis.2016.84 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by/4.0/ Oncogenesis is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Ding, J
Xie, M
Lian, Y
Zhu, Y
Peng, P
Wang, J
Wang, L
Wang, K
Long noncoding RNA HOXA-AS2 represses P21 and KLF2 expression transcription by binding with EZH2, LSD1 in colorectal cancer
title Long noncoding RNA HOXA-AS2 represses P21 and KLF2 expression transcription by binding with EZH2, LSD1 in colorectal cancer
title_full Long noncoding RNA HOXA-AS2 represses P21 and KLF2 expression transcription by binding with EZH2, LSD1 in colorectal cancer
title_fullStr Long noncoding RNA HOXA-AS2 represses P21 and KLF2 expression transcription by binding with EZH2, LSD1 in colorectal cancer
title_full_unstemmed Long noncoding RNA HOXA-AS2 represses P21 and KLF2 expression transcription by binding with EZH2, LSD1 in colorectal cancer
title_short Long noncoding RNA HOXA-AS2 represses P21 and KLF2 expression transcription by binding with EZH2, LSD1 in colorectal cancer
title_sort long noncoding rna hoxa-as2 represses p21 and klf2 expression transcription by binding with ezh2, lsd1 in colorectal cancer
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5294247/
https://www.ncbi.nlm.nih.gov/pubmed/28112720
http://dx.doi.org/10.1038/oncsis.2016.84
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