miR-4454 Promotes Hepatic Carcinoma Progression by Targeting Vps4A and Rab27A

Hepatocellular carcinoma (HCC) has high morbidity and mortality. MicroRNAs (miRNAs), which could be regulated by cancer-derived exosomes, play critical regulatory roles in the initiation and development of cancer. However, the expressions, effects, and mechanisms of abundant miRNAs regulated by HCC...

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Autores principales:	Haoming Lin, Rui Zhang, Wenrui Wu, Liming Lei
Formato:	article
Lenguaje:	EN
Publicado:	Hindawi Limited 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/620d28adf72940a7a3ca0fdcf89eaedf
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spelling	oai:doaj.org-article:620d28adf72940a7a3ca0fdcf89eaedf2021-11-15T01:20:06ZmiR-4454 Promotes Hepatic Carcinoma Progression by Targeting Vps4A and Rab27A1942-099410.1155/2021/9230435https://doaj.org/article/620d28adf72940a7a3ca0fdcf89eaedf2021-01-01T00:00:00Zhttp://dx.doi.org/10.1155/2021/9230435https://doaj.org/toc/1942-0994Hepatocellular carcinoma (HCC) has high morbidity and mortality. MicroRNAs (miRNAs), which could be regulated by cancer-derived exosomes, play critical regulatory roles in the initiation and development of cancer. However, the expressions, effects, and mechanisms of abundant miRNAs regulated by HCC cancer-derived exosomes in HCC remain largely unclear. Exosomes of HepG2 cells under heat shock, TGF-β1, doxorubicin, acid and hypoxia/reoxygenation (H/R) conditions, and exosomes were successfully identified by transmission electron microscopy and Western blot analysis. The identified exosomes were then applied to evaluate the miRNA expression profiles by RNA sequencing. Mechanically, we discovered that doxorubicin was upregulated, TGF-β1 downregulated the expressions of Vps4A, Rab27A, Alix, and Hrs in HepG2 cells and exosomes, and Vps4A and Rab27A, as target genes for miR-4454, could also be downregulated by miR-4454. Functionally, we revealed that miR-4454 inhibitor and miR-4454 inhibitor-mediated exosomes could markedly suppress proliferation, migration, invasion, and vascularization and accelerate cycle arrest, apoptosis, and ROS of HepG2 cells. This study provided many potential HCC cancer-derived exosome-mediated miRNAs in HCC under 5 different stimulus conditions. Meanwhile, we certified that miR-4454 in exosomes could provide a novel and effective mechanism for HCC function.Haoming LinRui ZhangWenrui WuLiming LeiHindawi LimitedarticleCytologyQH573-671ENOxidative Medicine and Cellular Longevity, Vol 2021 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Haoming Lin Rui Zhang Wenrui Wu Liming Lei miR-4454 Promotes Hepatic Carcinoma Progression by Targeting Vps4A and Rab27A
description	Hepatocellular carcinoma (HCC) has high morbidity and mortality. MicroRNAs (miRNAs), which could be regulated by cancer-derived exosomes, play critical regulatory roles in the initiation and development of cancer. However, the expressions, effects, and mechanisms of abundant miRNAs regulated by HCC cancer-derived exosomes in HCC remain largely unclear. Exosomes of HepG2 cells under heat shock, TGF-β1, doxorubicin, acid and hypoxia/reoxygenation (H/R) conditions, and exosomes were successfully identified by transmission electron microscopy and Western blot analysis. The identified exosomes were then applied to evaluate the miRNA expression profiles by RNA sequencing. Mechanically, we discovered that doxorubicin was upregulated, TGF-β1 downregulated the expressions of Vps4A, Rab27A, Alix, and Hrs in HepG2 cells and exosomes, and Vps4A and Rab27A, as target genes for miR-4454, could also be downregulated by miR-4454. Functionally, we revealed that miR-4454 inhibitor and miR-4454 inhibitor-mediated exosomes could markedly suppress proliferation, migration, invasion, and vascularization and accelerate cycle arrest, apoptosis, and ROS of HepG2 cells. This study provided many potential HCC cancer-derived exosome-mediated miRNAs in HCC under 5 different stimulus conditions. Meanwhile, we certified that miR-4454 in exosomes could provide a novel and effective mechanism for HCC function.
format	article
author	Haoming Lin Rui Zhang Wenrui Wu Liming Lei
author_facet	Haoming Lin Rui Zhang Wenrui Wu Liming Lei
author_sort	Haoming Lin
title	miR-4454 Promotes Hepatic Carcinoma Progression by Targeting Vps4A and Rab27A
title_short	miR-4454 Promotes Hepatic Carcinoma Progression by Targeting Vps4A and Rab27A
title_full	miR-4454 Promotes Hepatic Carcinoma Progression by Targeting Vps4A and Rab27A
title_fullStr	miR-4454 Promotes Hepatic Carcinoma Progression by Targeting Vps4A and Rab27A
title_full_unstemmed	miR-4454 Promotes Hepatic Carcinoma Progression by Targeting Vps4A and Rab27A
title_sort	mir-4454 promotes hepatic carcinoma progression by targeting vps4a and rab27a
publisher	Hindawi Limited
publishDate	2021
url	https://doaj.org/article/620d28adf72940a7a3ca0fdcf89eaedf
work_keys_str_mv	AT haominglin mir4454promoteshepaticcarcinomaprogressionbytargetingvps4aandrab27a AT ruizhang mir4454promoteshepaticcarcinomaprogressionbytargetingvps4aandrab27a AT wenruiwu mir4454promoteshepaticcarcinomaprogressionbytargetingvps4aandrab27a AT liminglei mir4454promoteshepaticcarcinomaprogressionbytargetingvps4aandrab27a
_version_	1718428925599678464

miR-4454 Promotes Hepatic Carcinoma Progression by Targeting Vps4A and Rab27A

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