Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1783321821186097152 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5944419 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American Society of Gene & Cell Therapy |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT zhaojuanfeng theash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma AT zhaoqiu theash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma AT huhui theash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma AT liaojiazhi theash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma AT linjusheng theash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma AT xiachao theash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma AT changying theash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma AT liujing theash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma AT guoanyuan theash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma AT hexingxing theash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma AT zhaojuanfeng ash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma AT zhaoqiu ash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma AT huhui ash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma AT liaojiazhi ash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma AT linjusheng ash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma AT xiachao ash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma AT changying ash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma AT liujing ash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma AT guoanyuan ash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma AT hexingxing ash1mir375ywhazsignalingaxisregulatestumorpropertiesinhepatocellularcarcinoma |