MicroRNA controlled adenovirus mediates anti-cancer efficacy without affecting endogenous microRNA activity.

MicroRNAs are small non-coding RNA molecules that regulate mRNA translation and stability by binding to complementary sequences usually within the 3' un-translated region (UTR). We have previously shown that the hepatic toxicity caused by wild-type Adenovirus 5 (Ad5WT) in mice can be prevented...

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Autores principales:	Ryan Cawood, Suet-Ling Wong, Ying Di, Dilair F Baban, Leonard W Seymour
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/31b27a319ae14a5fb78d650d87af5e7b
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spelling	oai:doaj.org-article:31b27a319ae14a5fb78d650d87af5e7b2021-11-18T07:00:36ZMicroRNA controlled adenovirus mediates anti-cancer efficacy without affecting endogenous microRNA activity.1932-620310.1371/journal.pone.0016152https://doaj.org/article/31b27a319ae14a5fb78d650d87af5e7b2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21264344/?tool=EBIhttps://doaj.org/toc/1932-6203MicroRNAs are small non-coding RNA molecules that regulate mRNA translation and stability by binding to complementary sequences usually within the 3' un-translated region (UTR). We have previously shown that the hepatic toxicity caused by wild-type Adenovirus 5 (Ad5WT) in mice can be prevented by incorporating 4 binding sites for the liver-specific microRNA, mir122, into the 3' UTR of E1A mRNA. This virus, termed Ad5mir122, is a promising virotherapy candidate and causes no obvious liver pathology. Herein we show that Ad5mir122 maintains wild-type lytic activity in cancer cells not expressing mir122 and assess any effects of possible mir122 depletion in host cells. Repeat administration of 2×10(10) viral particles of Admir122 to HepG2 tumour bearing mice showed significant anti-cancer efficacy. RT-QPCR showed that E1A mRNA was down-regulated 29-fold in liver when compared to Ad5WT. Western blot for E1A confirmed that all protein variants were knocked down. RT-QPCR for mature mir122 in infected livers showed that quantity of mir122 remained unaffected. Genome wide mRNA microarray profiling of infected livers showed that although the transcript level of >3900 different mRNAs changed more than 2-fold following Ad5WT infection, less than 600 were changed by Ad5mir122. These were then filtered to select mRNAs that were only altered by Ad5mir122 and the remaining 21 mRNAs were compared to predicted mir122 targets. No mir122 target mRNAs were affected by Ad5 mir122. These results demonstrate that the exploitation of microRNA regulation to control virus replication does not necessarily affect the level of the microRNA or the endogenous mRNA targets.Ryan CawoodSuet-Ling WongYing DiDilair F BabanLeonard W SeymourPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 1, p e16152 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ryan Cawood Suet-Ling Wong Ying Di Dilair F Baban Leonard W Seymour MicroRNA controlled adenovirus mediates anti-cancer efficacy without affecting endogenous microRNA activity.
description	MicroRNAs are small non-coding RNA molecules that regulate mRNA translation and stability by binding to complementary sequences usually within the 3' un-translated region (UTR). We have previously shown that the hepatic toxicity caused by wild-type Adenovirus 5 (Ad5WT) in mice can be prevented by incorporating 4 binding sites for the liver-specific microRNA, mir122, into the 3' UTR of E1A mRNA. This virus, termed Ad5mir122, is a promising virotherapy candidate and causes no obvious liver pathology. Herein we show that Ad5mir122 maintains wild-type lytic activity in cancer cells not expressing mir122 and assess any effects of possible mir122 depletion in host cells. Repeat administration of 2×10(10) viral particles of Admir122 to HepG2 tumour bearing mice showed significant anti-cancer efficacy. RT-QPCR showed that E1A mRNA was down-regulated 29-fold in liver when compared to Ad5WT. Western blot for E1A confirmed that all protein variants were knocked down. RT-QPCR for mature mir122 in infected livers showed that quantity of mir122 remained unaffected. Genome wide mRNA microarray profiling of infected livers showed that although the transcript level of >3900 different mRNAs changed more than 2-fold following Ad5WT infection, less than 600 were changed by Ad5mir122. These were then filtered to select mRNAs that were only altered by Ad5mir122 and the remaining 21 mRNAs were compared to predicted mir122 targets. No mir122 target mRNAs were affected by Ad5 mir122. These results demonstrate that the exploitation of microRNA regulation to control virus replication does not necessarily affect the level of the microRNA or the endogenous mRNA targets.
format	article
author	Ryan Cawood Suet-Ling Wong Ying Di Dilair F Baban Leonard W Seymour
author_facet	Ryan Cawood Suet-Ling Wong Ying Di Dilair F Baban Leonard W Seymour
author_sort	Ryan Cawood
title	MicroRNA controlled adenovirus mediates anti-cancer efficacy without affecting endogenous microRNA activity.
title_short	MicroRNA controlled adenovirus mediates anti-cancer efficacy without affecting endogenous microRNA activity.
title_full	MicroRNA controlled adenovirus mediates anti-cancer efficacy without affecting endogenous microRNA activity.
title_fullStr	MicroRNA controlled adenovirus mediates anti-cancer efficacy without affecting endogenous microRNA activity.
title_full_unstemmed	MicroRNA controlled adenovirus mediates anti-cancer efficacy without affecting endogenous microRNA activity.
title_sort	microrna controlled adenovirus mediates anti-cancer efficacy without affecting endogenous microrna activity.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/31b27a319ae14a5fb78d650d87af5e7b
work_keys_str_mv	AT ryancawood micrornacontrolledadenovirusmediatesanticancerefficacywithoutaffectingendogenousmicrornaactivity AT suetlingwong micrornacontrolledadenovirusmediatesanticancerefficacywithoutaffectingendogenousmicrornaactivity AT yingdi micrornacontrolledadenovirusmediatesanticancerefficacywithoutaffectingendogenousmicrornaactivity AT dilairfbaban micrornacontrolledadenovirusmediatesanticancerefficacywithoutaffectingendogenousmicrornaactivity AT leonardwseymour micrornacontrolledadenovirusmediatesanticancerefficacywithoutaffectingendogenousmicrornaactivity
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MicroRNA controlled adenovirus mediates anti-cancer efficacy without affecting endogenous microRNA activity.

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