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The ASH1-miR-375-YWHAZ Signaling Axis Regulates Tumor Properties in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is a worldwide malignance, and the underlying mechanisms of this disease are not fully elucidated. In this study, the existence and function of achaete-scute homolog-1 (ASH1)-miR-375-YWHAZ signaling axis in HCC were determined. Our experiments and the Cancer Genome Atl...

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Autores principales: Zhao, Juan-Feng, Zhao, Qiu, Hu, Hui, Liao, Jia-Zhi, Lin, Ju-Sheng, Xia, Chao, Chang, Ying, Liu, Jing, Guo, An-Yuan, He, Xing-Xing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944419/
https://www.ncbi.nlm.nih.gov/pubmed/29858089
http://dx.doi.org/10.1016/j.omtn.2018.04.007
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author Zhao, Juan-Feng
Zhao, Qiu
Hu, Hui
Liao, Jia-Zhi
Lin, Ju-Sheng
Xia, Chao
Chang, Ying
Liu, Jing
Guo, An-Yuan
He, Xing-Xing
author_facet Zhao, Juan-Feng
Zhao, Qiu
Hu, Hui
Liao, Jia-Zhi
Lin, Ju-Sheng
Xia, Chao
Chang, Ying
Liu, Jing
Guo, An-Yuan
He, Xing-Xing
author_sort Zhao, Juan-Feng
collection PubMed
description Hepatocellular carcinoma (HCC) is a worldwide malignance, and the underlying mechanisms of this disease are not fully elucidated. In this study, the existence and function of achaete-scute homolog-1 (ASH1)-miR-375-YWHAZ signaling axis in HCC were determined. Our experiments and the Cancer Genome Atlas (TCGA) sequencing data analyses showed that ASH1 and miR-375 were significantly downregulated, whereas YWHAZ was significantly upregulated in HCC. Furthermore, we found that ASH1 positively regulates miR-375, and miR-375 directly downregulates its target YWHAZ. Gain- and loss-of-function study demonstrated ASH1 and miR-375 function as tumor suppressors, whereas YWHAZ acts as an oncogene in HCC. Animal experiment indicated that YWHAZ small interfering RNAs (siRNAs) (si-YWHAZ) delivered by nanoliposomes could suppress the growth of hepatoma xenografts and was well tolerant by nude mice. Further studies revealed that YWHAZ was involved in several protein networks, such as cell autophagy, epithelial-mesenchymal transition (EMT), apoptosis, cell cycle, invasion, and migration. In addition, the patient group with ASH1-high-expression-miR-375-high-expression-YWHAZ-low-expression was correlated with a better clinical prognosis compared with the opposite expression group. In conclusion, we proved the existence of ASH1-miR-375-YWHAZ signaling axis and interpreted its important role in driving HCC tumor progression.
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spelling pubmed-59444192018-05-14 The ASH1-miR-375-YWHAZ Signaling Axis Regulates Tumor Properties in Hepatocellular Carcinoma Zhao, Juan-Feng Zhao, Qiu Hu, Hui Liao, Jia-Zhi Lin, Ju-Sheng Xia, Chao Chang, Ying Liu, Jing Guo, An-Yuan He, Xing-Xing Mol Ther Nucleic Acids Article Hepatocellular carcinoma (HCC) is a worldwide malignance, and the underlying mechanisms of this disease are not fully elucidated. In this study, the existence and function of achaete-scute homolog-1 (ASH1)-miR-375-YWHAZ signaling axis in HCC were determined. Our experiments and the Cancer Genome Atlas (TCGA) sequencing data analyses showed that ASH1 and miR-375 were significantly downregulated, whereas YWHAZ was significantly upregulated in HCC. Furthermore, we found that ASH1 positively regulates miR-375, and miR-375 directly downregulates its target YWHAZ. Gain- and loss-of-function study demonstrated ASH1 and miR-375 function as tumor suppressors, whereas YWHAZ acts as an oncogene in HCC. Animal experiment indicated that YWHAZ small interfering RNAs (siRNAs) (si-YWHAZ) delivered by nanoliposomes could suppress the growth of hepatoma xenografts and was well tolerant by nude mice. Further studies revealed that YWHAZ was involved in several protein networks, such as cell autophagy, epithelial-mesenchymal transition (EMT), apoptosis, cell cycle, invasion, and migration. In addition, the patient group with ASH1-high-expression-miR-375-high-expression-YWHAZ-low-expression was correlated with a better clinical prognosis compared with the opposite expression group. In conclusion, we proved the existence of ASH1-miR-375-YWHAZ signaling axis and interpreted its important role in driving HCC tumor progression. American Society of Gene & Cell Therapy 2018-04-25 /pmc/articles/PMC5944419/ /pubmed/29858089 http://dx.doi.org/10.1016/j.omtn.2018.04.007 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Zhao, Juan-Feng
Zhao, Qiu
Hu, Hui
Liao, Jia-Zhi
Lin, Ju-Sheng
Xia, Chao
Chang, Ying
Liu, Jing
Guo, An-Yuan
He, Xing-Xing
The ASH1-miR-375-YWHAZ Signaling Axis Regulates Tumor Properties in Hepatocellular Carcinoma
title The ASH1-miR-375-YWHAZ Signaling Axis Regulates Tumor Properties in Hepatocellular Carcinoma
title_full The ASH1-miR-375-YWHAZ Signaling Axis Regulates Tumor Properties in Hepatocellular Carcinoma
title_fullStr The ASH1-miR-375-YWHAZ Signaling Axis Regulates Tumor Properties in Hepatocellular Carcinoma
title_full_unstemmed The ASH1-miR-375-YWHAZ Signaling Axis Regulates Tumor Properties in Hepatocellular Carcinoma
title_short The ASH1-miR-375-YWHAZ Signaling Axis Regulates Tumor Properties in Hepatocellular Carcinoma
title_sort ash1-mir-375-ywhaz signaling axis regulates tumor properties in hepatocellular carcinoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944419/
https://www.ncbi.nlm.nih.gov/pubmed/29858089
http://dx.doi.org/10.1016/j.omtn.2018.04.007
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