KSHV microRNAs mediate cellular transformation and tumorigenesis by redundantly targeting cell growth and survival pathways.

Kaposi's sarcoma-associated herpesvirus (KSHV) is causally linked to several human cancers, including Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease, malignancies commonly found in HIV-infected patients. While KSHV encodes diverse functional products,...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Rosalie Moody, Ying Zhu, Yufei Huang, Xiaodong Cui, Tiffany Jones, Roble Bedolla, Xiufen Lei, Zhiqiang Bai, Shou-Jiang Gao
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a3e5e02a4aab4aa4af5ea1e4cffdfbd1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:a3e5e02a4aab4aa4af5ea1e4cffdfbd1
record_format	dspace
spelling	oai:doaj.org-article:a3e5e02a4aab4aa4af5ea1e4cffdfbd12021-11-18T06:07:10ZKSHV microRNAs mediate cellular transformation and tumorigenesis by redundantly targeting cell growth and survival pathways.1553-73661553-737410.1371/journal.ppat.1003857https://doaj.org/article/a3e5e02a4aab4aa4af5ea1e4cffdfbd12013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24385912/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Kaposi's sarcoma-associated herpesvirus (KSHV) is causally linked to several human cancers, including Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease, malignancies commonly found in HIV-infected patients. While KSHV encodes diverse functional products, its mechanism of oncogenesis remains unknown. In this study, we determined the roles KSHV microRNAs (miRs) in cellular transformation and tumorigenesis using a recently developed KSHV-induced cellular transformation system of primary rat mesenchymal precursor cells. A mutant with a cluster of 10 precursor miRs (pre-miRs) deleted failed to transform primary cells, and instead, caused cell cycle arrest and apoptosis. Remarkably, the oncogenicity of the mutant virus was fully restored by genetic complementation with the miR cluster or several individual pre-miRs, which rescued cell cycle progression and inhibited apoptosis in part by redundantly targeting IκBα and the NF-κB pathway. Genomic analysis identified common targets of KSHV miRs in diverse pathways with several cancer-related pathways preferentially targeted. These works define for the first time an essential viral determinant for KSHV-induced oncogenesis and identify NF-κB as a critical pathway targeted by the viral miRs. Our results illustrate a common theme of shared functions with hierarchical order among the KSHV miRs.Rosalie MoodyYing ZhuYufei HuangXiaodong CuiTiffany JonesRoble BedollaXiufen LeiZhiqiang BaiShou-Jiang GaoPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 12, p e1003857 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Rosalie Moody Ying Zhu Yufei Huang Xiaodong Cui Tiffany Jones Roble Bedolla Xiufen Lei Zhiqiang Bai Shou-Jiang Gao KSHV microRNAs mediate cellular transformation and tumorigenesis by redundantly targeting cell growth and survival pathways.
description	Kaposi's sarcoma-associated herpesvirus (KSHV) is causally linked to several human cancers, including Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease, malignancies commonly found in HIV-infected patients. While KSHV encodes diverse functional products, its mechanism of oncogenesis remains unknown. In this study, we determined the roles KSHV microRNAs (miRs) in cellular transformation and tumorigenesis using a recently developed KSHV-induced cellular transformation system of primary rat mesenchymal precursor cells. A mutant with a cluster of 10 precursor miRs (pre-miRs) deleted failed to transform primary cells, and instead, caused cell cycle arrest and apoptosis. Remarkably, the oncogenicity of the mutant virus was fully restored by genetic complementation with the miR cluster or several individual pre-miRs, which rescued cell cycle progression and inhibited apoptosis in part by redundantly targeting IκBα and the NF-κB pathway. Genomic analysis identified common targets of KSHV miRs in diverse pathways with several cancer-related pathways preferentially targeted. These works define for the first time an essential viral determinant for KSHV-induced oncogenesis and identify NF-κB as a critical pathway targeted by the viral miRs. Our results illustrate a common theme of shared functions with hierarchical order among the KSHV miRs.
format	article
author	Rosalie Moody Ying Zhu Yufei Huang Xiaodong Cui Tiffany Jones Roble Bedolla Xiufen Lei Zhiqiang Bai Shou-Jiang Gao
author_facet	Rosalie Moody Ying Zhu Yufei Huang Xiaodong Cui Tiffany Jones Roble Bedolla Xiufen Lei Zhiqiang Bai Shou-Jiang Gao
author_sort	Rosalie Moody
title	KSHV microRNAs mediate cellular transformation and tumorigenesis by redundantly targeting cell growth and survival pathways.
title_short	KSHV microRNAs mediate cellular transformation and tumorigenesis by redundantly targeting cell growth and survival pathways.
title_full	KSHV microRNAs mediate cellular transformation and tumorigenesis by redundantly targeting cell growth and survival pathways.
title_fullStr	KSHV microRNAs mediate cellular transformation and tumorigenesis by redundantly targeting cell growth and survival pathways.
title_full_unstemmed	KSHV microRNAs mediate cellular transformation and tumorigenesis by redundantly targeting cell growth and survival pathways.
title_sort	kshv micrornas mediate cellular transformation and tumorigenesis by redundantly targeting cell growth and survival pathways.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/a3e5e02a4aab4aa4af5ea1e4cffdfbd1
work_keys_str_mv	AT rosaliemoody kshvmicrornasmediatecellulartransformationandtumorigenesisbyredundantlytargetingcellgrowthandsurvivalpathways AT yingzhu kshvmicrornasmediatecellulartransformationandtumorigenesisbyredundantlytargetingcellgrowthandsurvivalpathways AT yufeihuang kshvmicrornasmediatecellulartransformationandtumorigenesisbyredundantlytargetingcellgrowthandsurvivalpathways AT xiaodongcui kshvmicrornasmediatecellulartransformationandtumorigenesisbyredundantlytargetingcellgrowthandsurvivalpathways AT tiffanyjones kshvmicrornasmediatecellulartransformationandtumorigenesisbyredundantlytargetingcellgrowthandsurvivalpathways AT roblebedolla kshvmicrornasmediatecellulartransformationandtumorigenesisbyredundantlytargetingcellgrowthandsurvivalpathways AT xiufenlei kshvmicrornasmediatecellulartransformationandtumorigenesisbyredundantlytargetingcellgrowthandsurvivalpathways AT zhiqiangbai kshvmicrornasmediatecellulartransformationandtumorigenesisbyredundantlytargetingcellgrowthandsurvivalpathways AT shoujianggao kshvmicrornasmediatecellulartransformationandtumorigenesisbyredundantlytargetingcellgrowthandsurvivalpathways
_version_	1718424557870645248

KSHV microRNAs mediate cellular transformation and tumorigenesis by redundantly targeting cell growth and survival pathways.

Ejemplares similares