LncRNA OIP5-AS1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors

Abstract Long non-coding RNAs (lncRNAs) play an important role in the regulation of key cellular processes in early development and cancer. LncRNA Oip5-as1 facilitates stem cell self-renewal in mouse by sponging mmu-miR-7 and modulating NANOG level, yet its role in cancer is less understood. We anal...

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Autores principales:	Ganesan Arunkumar, Shankar Anand, Partha Raksha, Shankar Dhamodharan, Harikrishnan Prasanna Srinivasa Rao, Shanmugam Subbiah, Avaniyapuram Kannan Murugan, Arasambattu Kannan Munirajan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3ba9c4d7802b420d8db868eb1877473f
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spelling	oai:doaj.org-article:3ba9c4d7802b420d8db868eb1877473f2021-12-02T11:41:23ZLncRNA OIP5-AS1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors10.1038/s41598-018-25451-32045-2322https://doaj.org/article/3ba9c4d7802b420d8db868eb1877473f2018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25451-3https://doaj.org/toc/2045-2322Abstract Long non-coding RNAs (lncRNAs) play an important role in the regulation of key cellular processes in early development and cancer. LncRNA Oip5-as1 facilitates stem cell self-renewal in mouse by sponging mmu-miR-7 and modulating NANOG level, yet its role in cancer is less understood. We analyzed OIP5-AS1 expression in oral tumors and in TCGA datasets. We observed overexpression of OIP5-AS1 in oral tumors (P < 0.001) and in tumors of epithelial origin from TCGA. OIP5-AS1 expression was strongly associated with undifferentiated tumors (P = 0.0038). In silico analysis showed miR-7 binding site is conserved in mouse and human OIP5-AS1. However, human NANOG 3′-UTR lost the binding site for hsa-miR-7a-3. Therefore, we screened for other miRNAs that can be sponged by OIP5-AS1 and identified six potential miRNAs and their downstream target genes. Expression analysis showed downregulation of miRNAs and upregulation of downstream target genes, particularly in undifferentiated tumors with high-level of OIP5-AS1 suggesting OIP5-AS1 could post-transcriptionally modulate the downstream target genes. Further, systematic epigenomic analysis of OIP5-AS1 promoter revealed binding motifs for MYC, NANOG and KLF4 suggesting that OIP5-AS1 could be transactivated by stemness-associated transcription factors in cancer. OIP5-AS1 overexpression in undifferentiated oral tumors may be suggestive of enhanced cancer stemness, and consequently, poor clinical outcome.Ganesan ArunkumarShankar AnandPartha RakshaShankar DhamodharanHarikrishnan Prasanna Srinivasa RaoShanmugam SubbiahAvaniyapuram Kannan MuruganArasambattu Kannan MunirajanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-13 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ganesan Arunkumar Shankar Anand Partha Raksha Shankar Dhamodharan Harikrishnan Prasanna Srinivasa Rao Shanmugam Subbiah Avaniyapuram Kannan Murugan Arasambattu Kannan Munirajan LncRNA OIP5-AS1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors
description	Abstract Long non-coding RNAs (lncRNAs) play an important role in the regulation of key cellular processes in early development and cancer. LncRNA Oip5-as1 facilitates stem cell self-renewal in mouse by sponging mmu-miR-7 and modulating NANOG level, yet its role in cancer is less understood. We analyzed OIP5-AS1 expression in oral tumors and in TCGA datasets. We observed overexpression of OIP5-AS1 in oral tumors (P < 0.001) and in tumors of epithelial origin from TCGA. OIP5-AS1 expression was strongly associated with undifferentiated tumors (P = 0.0038). In silico analysis showed miR-7 binding site is conserved in mouse and human OIP5-AS1. However, human NANOG 3′-UTR lost the binding site for hsa-miR-7a-3. Therefore, we screened for other miRNAs that can be sponged by OIP5-AS1 and identified six potential miRNAs and their downstream target genes. Expression analysis showed downregulation of miRNAs and upregulation of downstream target genes, particularly in undifferentiated tumors with high-level of OIP5-AS1 suggesting OIP5-AS1 could post-transcriptionally modulate the downstream target genes. Further, systematic epigenomic analysis of OIP5-AS1 promoter revealed binding motifs for MYC, NANOG and KLF4 suggesting that OIP5-AS1 could be transactivated by stemness-associated transcription factors in cancer. OIP5-AS1 overexpression in undifferentiated oral tumors may be suggestive of enhanced cancer stemness, and consequently, poor clinical outcome.
format	article
author	Ganesan Arunkumar Shankar Anand Partha Raksha Shankar Dhamodharan Harikrishnan Prasanna Srinivasa Rao Shanmugam Subbiah Avaniyapuram Kannan Murugan Arasambattu Kannan Munirajan
author_facet	Ganesan Arunkumar Shankar Anand Partha Raksha Shankar Dhamodharan Harikrishnan Prasanna Srinivasa Rao Shanmugam Subbiah Avaniyapuram Kannan Murugan Arasambattu Kannan Munirajan
author_sort	Ganesan Arunkumar
title	LncRNA OIP5-AS1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors
title_short	LncRNA OIP5-AS1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors
title_full	LncRNA OIP5-AS1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors
title_fullStr	LncRNA OIP5-AS1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors
title_full_unstemmed	LncRNA OIP5-AS1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors
title_sort	lncrna oip5-as1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/3ba9c4d7802b420d8db868eb1877473f
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LncRNA OIP5-AS1 is overexpressed in undifferentiated oral tumors and integrated analysis identifies as a downstream effector of stemness-associated transcription factors

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