A feedback inhibition between miRNA-127 and TGFβ/c-Jun cascade in HCC cell migration via MMP13.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and is increasing in frequency in the U.S. The major reason for the low postoperative survival rate of HCC is widespread intrahepatic metastasis or invasion, and activation of TGFβ signaling is associated with the invasive phen...

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Autores principales:	Zhihong Yang, Yuxia Zhang, Li Wang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c132c6303cbb4e4eabd57666650e1cc5
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spelling	oai:doaj.org-article:c132c6303cbb4e4eabd57666650e1cc52021-11-18T07:42:38ZA feedback inhibition between miRNA-127 and TGFβ/c-Jun cascade in HCC cell migration via MMP13.1932-620310.1371/journal.pone.0065256https://doaj.org/article/c132c6303cbb4e4eabd57666650e1cc52013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23762330/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and is increasing in frequency in the U.S. The major reason for the low postoperative survival rate of HCC is widespread intrahepatic metastasis or invasion, and activation of TGFβ signaling is associated with the invasive phenotype. This study aims at determining the novel function of miR-127 in modulating HCC migration. Overexpression of miR-127 inhibits HCC cell migration, invasion and tumor growth in nude mice. MiR-127 directly represses matrix metalloproteinase 13 (MMP13) 3'UTR activity and protein expression, and diminishes MMP13/TGFβ-induced HCC migration. In turn, TGFβ decreases miR-127 expression by enhancing c-Jun-mediated inhibition of miR-127 promoter activity. In contrast, p53 transactivates miR-127 promoter and induces miR-127 expression, which is antagonized by c-Jun. The inhibition of miR-127 by c-Jun is through TGFβ-mediated ERK and JNK pathways. The lower miR-127 expression shows a negative correlation with the higher MMP13 expression in a subset of human HCC specimens. This is the first report elucidating a feedback regulation between miR-127 and the TGFβ/c-Jun cascade in HCC migration via MMP13 that involves a crosstalk between the oncogene c-Jun and tumor suppressor p53.Zhihong YangYuxia ZhangLi WangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 6, p e65256 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zhihong Yang Yuxia Zhang Li Wang A feedback inhibition between miRNA-127 and TGFβ/c-Jun cascade in HCC cell migration via MMP13.
description	Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and is increasing in frequency in the U.S. The major reason for the low postoperative survival rate of HCC is widespread intrahepatic metastasis or invasion, and activation of TGFβ signaling is associated with the invasive phenotype. This study aims at determining the novel function of miR-127 in modulating HCC migration. Overexpression of miR-127 inhibits HCC cell migration, invasion and tumor growth in nude mice. MiR-127 directly represses matrix metalloproteinase 13 (MMP13) 3'UTR activity and protein expression, and diminishes MMP13/TGFβ-induced HCC migration. In turn, TGFβ decreases miR-127 expression by enhancing c-Jun-mediated inhibition of miR-127 promoter activity. In contrast, p53 transactivates miR-127 promoter and induces miR-127 expression, which is antagonized by c-Jun. The inhibition of miR-127 by c-Jun is through TGFβ-mediated ERK and JNK pathways. The lower miR-127 expression shows a negative correlation with the higher MMP13 expression in a subset of human HCC specimens. This is the first report elucidating a feedback regulation between miR-127 and the TGFβ/c-Jun cascade in HCC migration via MMP13 that involves a crosstalk between the oncogene c-Jun and tumor suppressor p53.
format	article
author	Zhihong Yang Yuxia Zhang Li Wang
author_facet	Zhihong Yang Yuxia Zhang Li Wang
author_sort	Zhihong Yang
title	A feedback inhibition between miRNA-127 and TGFβ/c-Jun cascade in HCC cell migration via MMP13.
title_short	A feedback inhibition between miRNA-127 and TGFβ/c-Jun cascade in HCC cell migration via MMP13.
title_full	A feedback inhibition between miRNA-127 and TGFβ/c-Jun cascade in HCC cell migration via MMP13.
title_fullStr	A feedback inhibition between miRNA-127 and TGFβ/c-Jun cascade in HCC cell migration via MMP13.
title_full_unstemmed	A feedback inhibition between miRNA-127 and TGFβ/c-Jun cascade in HCC cell migration via MMP13.
title_sort	feedback inhibition between mirna-127 and tgfβ/c-jun cascade in hcc cell migration via mmp13.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/c132c6303cbb4e4eabd57666650e1cc5
work_keys_str_mv	AT zhihongyang afeedbackinhibitionbetweenmirna127andtgfbcjuncascadeinhcccellmigrationviammp13 AT yuxiazhang afeedbackinhibitionbetweenmirna127andtgfbcjuncascadeinhcccellmigrationviammp13 AT liwang afeedbackinhibitionbetweenmirna127andtgfbcjuncascadeinhcccellmigrationviammp13 AT zhihongyang feedbackinhibitionbetweenmirna127andtgfbcjuncascadeinhcccellmigrationviammp13 AT yuxiazhang feedbackinhibitionbetweenmirna127andtgfbcjuncascadeinhcccellmigrationviammp13 AT liwang feedbackinhibitionbetweenmirna127andtgfbcjuncascadeinhcccellmigrationviammp13
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A feedback inhibition between miRNA-127 and TGFβ/c-Jun cascade in HCC cell migration via MMP13.

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