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miR-96 regulates liver tumor-initiating cells expansion by targeting TP53INP1 and predicts Sorafenib resistance

Liver tumor-initiating cells (T-ICs) contribute to tumorigenesis, progression, recurrence and drug resistance of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver T-ICs remains unclear. In the present study, our finding shows that miR-96 is upregulated in...

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Autores principales: Huang, Yonggang, Zhang, Jin, Li, HengYu, Peng, Huiping, Gu, Maolin, Wang, Hengjie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545665/
https://www.ncbi.nlm.nih.gov/pubmed/33046975
http://dx.doi.org/10.7150/jca.48333
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author Huang, Yonggang
Zhang, Jin
Li, HengYu
Peng, Huiping
Gu, Maolin
Wang, Hengjie
author_facet Huang, Yonggang
Zhang, Jin
Li, HengYu
Peng, Huiping
Gu, Maolin
Wang, Hengjie
author_sort Huang, Yonggang
collection PubMed
description Liver tumor-initiating cells (T-ICs) contribute to tumorigenesis, progression, recurrence and drug resistance of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver T-ICs remains unclear. In the present study, our finding shows that miR-96 is upregulated in liver T-ICs. Functional studies revealed that forced miR-96 promotes liver T-ICs self-renewal and tumorigenesis. Conversely, knockdown miR-96 inhibits liver T-ICs self-renewal and tumorigenesis. Mechanistically, miR-96 downregulates TP53INP1 via its mRNA 3'UTR in liver T-ICs. Furthermore, the miR-96 expression determines the responses of hepatoma cells to sorafenib treatment. Analysis of patient cohorts and patient-derived xenografts (PDXs) further demonstrate that the miR-96 may predict sorafenib benefits in HCC patients. Our findings revealed the crucial role of the miR-96 in liver T-ICs expansion and sorafenib response, rendering miR-96 as an optimal target for the prevention and intervention of HCC.
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spelling pubmed-75456652020-10-11 miR-96 regulates liver tumor-initiating cells expansion by targeting TP53INP1 and predicts Sorafenib resistance Huang, Yonggang Zhang, Jin Li, HengYu Peng, Huiping Gu, Maolin Wang, Hengjie J Cancer Research Paper Liver tumor-initiating cells (T-ICs) contribute to tumorigenesis, progression, recurrence and drug resistance of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver T-ICs remains unclear. In the present study, our finding shows that miR-96 is upregulated in liver T-ICs. Functional studies revealed that forced miR-96 promotes liver T-ICs self-renewal and tumorigenesis. Conversely, knockdown miR-96 inhibits liver T-ICs self-renewal and tumorigenesis. Mechanistically, miR-96 downregulates TP53INP1 via its mRNA 3'UTR in liver T-ICs. Furthermore, the miR-96 expression determines the responses of hepatoma cells to sorafenib treatment. Analysis of patient cohorts and patient-derived xenografts (PDXs) further demonstrate that the miR-96 may predict sorafenib benefits in HCC patients. Our findings revealed the crucial role of the miR-96 in liver T-ICs expansion and sorafenib response, rendering miR-96 as an optimal target for the prevention and intervention of HCC. Ivyspring International Publisher 2020-09-21 /pmc/articles/PMC7545665/ /pubmed/33046975 http://dx.doi.org/10.7150/jca.48333 Text en © The author(s) This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Huang, Yonggang
Zhang, Jin
Li, HengYu
Peng, Huiping
Gu, Maolin
Wang, Hengjie
miR-96 regulates liver tumor-initiating cells expansion by targeting TP53INP1 and predicts Sorafenib resistance
title miR-96 regulates liver tumor-initiating cells expansion by targeting TP53INP1 and predicts Sorafenib resistance
title_full miR-96 regulates liver tumor-initiating cells expansion by targeting TP53INP1 and predicts Sorafenib resistance
title_fullStr miR-96 regulates liver tumor-initiating cells expansion by targeting TP53INP1 and predicts Sorafenib resistance
title_full_unstemmed miR-96 regulates liver tumor-initiating cells expansion by targeting TP53INP1 and predicts Sorafenib resistance
title_short miR-96 regulates liver tumor-initiating cells expansion by targeting TP53INP1 and predicts Sorafenib resistance
title_sort mir-96 regulates liver tumor-initiating cells expansion by targeting tp53inp1 and predicts sorafenib resistance
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545665/
https://www.ncbi.nlm.nih.gov/pubmed/33046975
http://dx.doi.org/10.7150/jca.48333
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