Roles of PI3K/Akt and c-Jun signaling pathways in human papillomavirus type 16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis in non-small cell lung cancer cells.

<h4>Background and objectives</h4>Human papillomavirus (HPV)-16 infection may be related to non-smoking associated lung cancer. Our previous studies have found that HPV-16 oncoproteins promoted angiogenesis via enhancing hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth f...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Erying Zhang, Xiaowei Feng, Fei Liu, Peihua Zhang, Jie Liang, Xudong Tang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/09edfb4378c54e18a36562b6c4b13b14
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:09edfb4378c54e18a36562b6c4b13b14
record_format	dspace
spelling	oai:doaj.org-article:09edfb4378c54e18a36562b6c4b13b142021-11-25T06:07:14ZRoles of PI3K/Akt and c-Jun signaling pathways in human papillomavirus type 16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis in non-small cell lung cancer cells.1932-620310.1371/journal.pone.0103440https://doaj.org/article/09edfb4378c54e18a36562b6c4b13b142014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25058399/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background and objectives</h4>Human papillomavirus (HPV)-16 infection may be related to non-smoking associated lung cancer. Our previous studies have found that HPV-16 oncoproteins promoted angiogenesis via enhancing hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) expression in non-small cell lung cancer (NSCLC) cells. In this study, we further investigated the roles of PI3K/Akt and c-Jun signaling pathways in it.<h4>Methods</h4>Human NSCLC cell lines, A549 and NCI-H460, were stably transfected with pEGFP-16 E6 or E7 plasmids. Western blotting was performed to analyze the expression of HIF-1α, p-Akt, p-P70S6K, p-P85S6K, p-mTOR, p-JNK, and p-c-Jun proteins. VEGF and IL-8 protein secretion and mRNA levels were determined by ELISA and Real-time PCR, respectively. The in vitro angiogenesis was observed by human umbilical vein endothelial cells (HUVECs) tube formation assay. Co-immunoprecipitation was performed to analyze the interaction between c-Jun and HIF-1α.<h4>Results</h4>HPV-16 E6 and E7 oncoproteins promoted the activation of Akt, P70S6K, P85S6K, mTOR, JNK, and c-Jun. LY294002, a PI3K inhibitor, inhibited HPV-16 oncoprotein-induced activation of Akt, P70S6K, and P85S6K, expression of HIF-1α, VEGF, and IL-8, and in vitro angiogenesis. c-Jun knockdown by specific siRNA abolished HPV-16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis. Additionally, HPV-16 oncoproteins promoted HIF-1α protein stability via blocking proteasome degradation pathway, but c-Jun knockdown abrogated this effect. Furthermore, HPV-16 oncoproteins increased the quantity of c-Jun binding to HIF-1α.<h4>Conclusions</h4>PI3K/Akt signaling pathway and c-Jun are involved in HPV-16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis. Moreover, HPV-16 oncoproteins promoted HIF-1α protein stability possibly through enhancing the interaction between c-Jun and HIF-1α, thus making a contribution to angiogenesis in NSCLC cells.Erying ZhangXiaowei FengFei LiuPeihua ZhangJie LiangXudong TangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e103440 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Erying Zhang Xiaowei Feng Fei Liu Peihua Zhang Jie Liang Xudong Tang Roles of PI3K/Akt and c-Jun signaling pathways in human papillomavirus type 16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis in non-small cell lung cancer cells.
description	<h4>Background and objectives</h4>Human papillomavirus (HPV)-16 infection may be related to non-smoking associated lung cancer. Our previous studies have found that HPV-16 oncoproteins promoted angiogenesis via enhancing hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and interleukin-8 (IL-8) expression in non-small cell lung cancer (NSCLC) cells. In this study, we further investigated the roles of PI3K/Akt and c-Jun signaling pathways in it.<h4>Methods</h4>Human NSCLC cell lines, A549 and NCI-H460, were stably transfected with pEGFP-16 E6 or E7 plasmids. Western blotting was performed to analyze the expression of HIF-1α, p-Akt, p-P70S6K, p-P85S6K, p-mTOR, p-JNK, and p-c-Jun proteins. VEGF and IL-8 protein secretion and mRNA levels were determined by ELISA and Real-time PCR, respectively. The in vitro angiogenesis was observed by human umbilical vein endothelial cells (HUVECs) tube formation assay. Co-immunoprecipitation was performed to analyze the interaction between c-Jun and HIF-1α.<h4>Results</h4>HPV-16 E6 and E7 oncoproteins promoted the activation of Akt, P70S6K, P85S6K, mTOR, JNK, and c-Jun. LY294002, a PI3K inhibitor, inhibited HPV-16 oncoprotein-induced activation of Akt, P70S6K, and P85S6K, expression of HIF-1α, VEGF, and IL-8, and in vitro angiogenesis. c-Jun knockdown by specific siRNA abolished HPV-16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis. Additionally, HPV-16 oncoproteins promoted HIF-1α protein stability via blocking proteasome degradation pathway, but c-Jun knockdown abrogated this effect. Furthermore, HPV-16 oncoproteins increased the quantity of c-Jun binding to HIF-1α.<h4>Conclusions</h4>PI3K/Akt signaling pathway and c-Jun are involved in HPV-16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis. Moreover, HPV-16 oncoproteins promoted HIF-1α protein stability possibly through enhancing the interaction between c-Jun and HIF-1α, thus making a contribution to angiogenesis in NSCLC cells.
format	article
author	Erying Zhang Xiaowei Feng Fei Liu Peihua Zhang Jie Liang Xudong Tang
author_facet	Erying Zhang Xiaowei Feng Fei Liu Peihua Zhang Jie Liang Xudong Tang
author_sort	Erying Zhang
title	Roles of PI3K/Akt and c-Jun signaling pathways in human papillomavirus type 16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis in non-small cell lung cancer cells.
title_short	Roles of PI3K/Akt and c-Jun signaling pathways in human papillomavirus type 16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis in non-small cell lung cancer cells.
title_full	Roles of PI3K/Akt and c-Jun signaling pathways in human papillomavirus type 16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis in non-small cell lung cancer cells.
title_fullStr	Roles of PI3K/Akt and c-Jun signaling pathways in human papillomavirus type 16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis in non-small cell lung cancer cells.
title_full_unstemmed	Roles of PI3K/Akt and c-Jun signaling pathways in human papillomavirus type 16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis in non-small cell lung cancer cells.
title_sort	roles of pi3k/akt and c-jun signaling pathways in human papillomavirus type 16 oncoprotein-induced hif-1α, vegf, and il-8 expression and in vitro angiogenesis in non-small cell lung cancer cells.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/09edfb4378c54e18a36562b6c4b13b14
work_keys_str_mv	AT eryingzhang rolesofpi3kaktandcjunsignalingpathwaysinhumanpapillomavirustype16oncoproteininducedhif1avegfandil8expressionandinvitroangiogenesisinnonsmallcelllungcancercells AT xiaoweifeng rolesofpi3kaktandcjunsignalingpathwaysinhumanpapillomavirustype16oncoproteininducedhif1avegfandil8expressionandinvitroangiogenesisinnonsmallcelllungcancercells AT feiliu rolesofpi3kaktandcjunsignalingpathwaysinhumanpapillomavirustype16oncoproteininducedhif1avegfandil8expressionandinvitroangiogenesisinnonsmallcelllungcancercells AT peihuazhang rolesofpi3kaktandcjunsignalingpathwaysinhumanpapillomavirustype16oncoproteininducedhif1avegfandil8expressionandinvitroangiogenesisinnonsmallcelllungcancercells AT jieliang rolesofpi3kaktandcjunsignalingpathwaysinhumanpapillomavirustype16oncoproteininducedhif1avegfandil8expressionandinvitroangiogenesisinnonsmallcelllungcancercells AT xudongtang rolesofpi3kaktandcjunsignalingpathwaysinhumanpapillomavirustype16oncoproteininducedhif1avegfandil8expressionandinvitroangiogenesisinnonsmallcelllungcancercells
_version_	1718414146381283328

Roles of PI3K/Akt and c-Jun signaling pathways in human papillomavirus type 16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis in non-small cell lung cancer cells.

Ejemplares similares