Cargando…

The lncRNA HMS recruits RNA-binding protein HuR to stabilize the 3′-UTR of HOXC10 mRNA

Long noncoding RNAs (lncRNAs) have been reported to drive key cancer pathways but the functions of majority of lncRNAs are unknown making a case for comprehensive functional evaluation of lncRNAs. With an aim to identify lncRNAs dysregulated in human cancers, we analyzed the cancer patient database...

Descripción completa

Detalles Bibliográficos
Autores principales: Priyanka, Priyanka, Sharma, Madhur, Das, Sanjeev, Saxena, Sandeep
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363838/
https://www.ncbi.nlm.nih.gov/pubmed/34302808
http://dx.doi.org/10.1016/j.jbc.2021.100997
_version_ 1783738418440699904
author Priyanka, Priyanka
Sharma, Madhur
Das, Sanjeev
Saxena, Sandeep
author_facet Priyanka, Priyanka
Sharma, Madhur
Das, Sanjeev
Saxena, Sandeep
author_sort Priyanka, Priyanka
collection PubMed
description Long noncoding RNAs (lncRNAs) have been reported to drive key cancer pathways but the functions of majority of lncRNAs are unknown making a case for comprehensive functional evaluation of lncRNAs. With an aim to identify lncRNAs dysregulated in human cancers, we analyzed the cancer patient database of lung adenocarcinoma (LUAD), which revealed an upregulated lncRNA, LINC02381 (renamed HOXC10mRNA stabilizing factor or HMS in this study), whose depletion results in proliferation defects and inhibition of colony formation of human cancer cells. In order to identify the binding targets of HMS, we screened for cis-genes and discovered that HOXC10, an oncogene, is downregulated in the absence of HMS. Depletion of HMS does not affect the HOXC10 promoter activity but inhibits the HOXC10 3′-UTR-linked luciferase reporter activity. Since lncRNAs have been known to associate with RNA-binding proteins (RBPs) to stabilize mRNA transcripts, we screened for different RBPs and discovered that HuR, an ELAV family protein, stabilizes HOXC10 mRNA. Using RNA pull-down and deletion mapping experiments, we show that HuR physically interacts with the cytosine-rich stretch of HMS and HOXC10 3′-UTR to stabilize HOXC10 mRNA. HOXC10 is overexpressed in many human cancers, and our discovery highlights that lncRNA HMS sustains the HOXC10 mRNA levels to maintain the invasive phenotypes of cancer cells.
format Online
Article
Text
id pubmed-8363838
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher American Society for Biochemistry and Molecular Biology
record_format MEDLINE/PubMed
spelling pubmed-83638382021-08-23 The lncRNA HMS recruits RNA-binding protein HuR to stabilize the 3′-UTR of HOXC10 mRNA Priyanka, Priyanka Sharma, Madhur Das, Sanjeev Saxena, Sandeep J Biol Chem Research Article Long noncoding RNAs (lncRNAs) have been reported to drive key cancer pathways but the functions of majority of lncRNAs are unknown making a case for comprehensive functional evaluation of lncRNAs. With an aim to identify lncRNAs dysregulated in human cancers, we analyzed the cancer patient database of lung adenocarcinoma (LUAD), which revealed an upregulated lncRNA, LINC02381 (renamed HOXC10mRNA stabilizing factor or HMS in this study), whose depletion results in proliferation defects and inhibition of colony formation of human cancer cells. In order to identify the binding targets of HMS, we screened for cis-genes and discovered that HOXC10, an oncogene, is downregulated in the absence of HMS. Depletion of HMS does not affect the HOXC10 promoter activity but inhibits the HOXC10 3′-UTR-linked luciferase reporter activity. Since lncRNAs have been known to associate with RNA-binding proteins (RBPs) to stabilize mRNA transcripts, we screened for different RBPs and discovered that HuR, an ELAV family protein, stabilizes HOXC10 mRNA. Using RNA pull-down and deletion mapping experiments, we show that HuR physically interacts with the cytosine-rich stretch of HMS and HOXC10 3′-UTR to stabilize HOXC10 mRNA. HOXC10 is overexpressed in many human cancers, and our discovery highlights that lncRNA HMS sustains the HOXC10 mRNA levels to maintain the invasive phenotypes of cancer cells. American Society for Biochemistry and Molecular Biology 2021-07-22 /pmc/articles/PMC8363838/ /pubmed/34302808 http://dx.doi.org/10.1016/j.jbc.2021.100997 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Research Article
Priyanka, Priyanka
Sharma, Madhur
Das, Sanjeev
Saxena, Sandeep
The lncRNA HMS recruits RNA-binding protein HuR to stabilize the 3′-UTR of HOXC10 mRNA
title The lncRNA HMS recruits RNA-binding protein HuR to stabilize the 3′-UTR of HOXC10 mRNA
title_full The lncRNA HMS recruits RNA-binding protein HuR to stabilize the 3′-UTR of HOXC10 mRNA
title_fullStr The lncRNA HMS recruits RNA-binding protein HuR to stabilize the 3′-UTR of HOXC10 mRNA
title_full_unstemmed The lncRNA HMS recruits RNA-binding protein HuR to stabilize the 3′-UTR of HOXC10 mRNA
title_short The lncRNA HMS recruits RNA-binding protein HuR to stabilize the 3′-UTR of HOXC10 mRNA
title_sort lncrna hms recruits rna-binding protein hur to stabilize the 3′-utr of hoxc10 mrna
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363838/
https://www.ncbi.nlm.nih.gov/pubmed/34302808
http://dx.doi.org/10.1016/j.jbc.2021.100997
work_keys_str_mv AT priyankapriyanka thelncrnahmsrecruitsrnabindingproteinhurtostabilizethe3utrofhoxc10mrna
AT sharmamadhur thelncrnahmsrecruitsrnabindingproteinhurtostabilizethe3utrofhoxc10mrna
AT dassanjeev thelncrnahmsrecruitsrnabindingproteinhurtostabilizethe3utrofhoxc10mrna
AT saxenasandeep thelncrnahmsrecruitsrnabindingproteinhurtostabilizethe3utrofhoxc10mrna
AT priyankapriyanka lncrnahmsrecruitsrnabindingproteinhurtostabilizethe3utrofhoxc10mrna
AT sharmamadhur lncrnahmsrecruitsrnabindingproteinhurtostabilizethe3utrofhoxc10mrna
AT dassanjeev lncrnahmsrecruitsrnabindingproteinhurtostabilizethe3utrofhoxc10mrna
AT saxenasandeep lncrnahmsrecruitsrnabindingproteinhurtostabilizethe3utrofhoxc10mrna