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HNRNPH1 Is a Novel Regulator Of Cellular Proliferation and Disease Progression in Chronic Myeloid Leukemia

RNA binding proteins act as essential modulators in cancers by regulating biological cellular processes. Heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1), as a key member of the heterogeneous nuclear ribonucleoproteins family, is frequently upregulated in multiple cancer cells and involved in tu...

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Autores principales: Liu, Menghan, Yang, Lin, Liu, Xiaojun, Nie, Ziyuan, Zhang, Xiaoyan, Lu, Yaqiong, Pan, Yuxia, Wang, Xingzhe, Luo, Jianmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290130/
https://www.ncbi.nlm.nih.gov/pubmed/34295818
http://dx.doi.org/10.3389/fonc.2021.682859
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author Liu, Menghan
Yang, Lin
Liu, Xiaojun
Nie, Ziyuan
Zhang, Xiaoyan
Lu, Yaqiong
Pan, Yuxia
Wang, Xingzhe
Luo, Jianmin
author_facet Liu, Menghan
Yang, Lin
Liu, Xiaojun
Nie, Ziyuan
Zhang, Xiaoyan
Lu, Yaqiong
Pan, Yuxia
Wang, Xingzhe
Luo, Jianmin
author_sort Liu, Menghan
collection PubMed
description RNA binding proteins act as essential modulators in cancers by regulating biological cellular processes. Heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1), as a key member of the heterogeneous nuclear ribonucleoproteins family, is frequently upregulated in multiple cancer cells and involved in tumorigenesis. However, the function of HNRNPH1 in chronic myeloid leukemia (CML) remains unclear. In the present study, we revealed that HNRNPH1 expression level was upregulated in CML patients and cell lines. Moreover, the higher level of HNRNPH1 was correlated with disease progression of CML. In vivo and in vitro experiments showed that knockdown of HNRNPH1 inhibited cell proliferation and promoted cell apoptosis in CML cells. Importantly, knockdown of HNRNPH1 in CML cells enhanced sensitivity to imatinib. Mechanically, HNRNPH1 could bind to the mRNA of PTPN6 and negatively regulated its expression. PTPN6 mediated the regulation between HNRNPH1 and PI3K/AKT activation. Furthermore, the HNRNPH1–PTPN6–PI3K/AKT axis played a critical role in CML tumorigenesis and development. The present study first investigated the deregulated HNRNPH1–PTPN6–PI3K/AKT axis moderated cell growth and apoptosis in CML cells, whereby targeting this pathway may be a therapeutic CML treatment.
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spelling pubmed-82901302021-07-21 HNRNPH1 Is a Novel Regulator Of Cellular Proliferation and Disease Progression in Chronic Myeloid Leukemia Liu, Menghan Yang, Lin Liu, Xiaojun Nie, Ziyuan Zhang, Xiaoyan Lu, Yaqiong Pan, Yuxia Wang, Xingzhe Luo, Jianmin Front Oncol Oncology RNA binding proteins act as essential modulators in cancers by regulating biological cellular processes. Heterogeneous nuclear ribonucleoprotein H1 (HNRNPH1), as a key member of the heterogeneous nuclear ribonucleoproteins family, is frequently upregulated in multiple cancer cells and involved in tumorigenesis. However, the function of HNRNPH1 in chronic myeloid leukemia (CML) remains unclear. In the present study, we revealed that HNRNPH1 expression level was upregulated in CML patients and cell lines. Moreover, the higher level of HNRNPH1 was correlated with disease progression of CML. In vivo and in vitro experiments showed that knockdown of HNRNPH1 inhibited cell proliferation and promoted cell apoptosis in CML cells. Importantly, knockdown of HNRNPH1 in CML cells enhanced sensitivity to imatinib. Mechanically, HNRNPH1 could bind to the mRNA of PTPN6 and negatively regulated its expression. PTPN6 mediated the regulation between HNRNPH1 and PI3K/AKT activation. Furthermore, the HNRNPH1–PTPN6–PI3K/AKT axis played a critical role in CML tumorigenesis and development. The present study first investigated the deregulated HNRNPH1–PTPN6–PI3K/AKT axis moderated cell growth and apoptosis in CML cells, whereby targeting this pathway may be a therapeutic CML treatment. Frontiers Media S.A. 2021-07-06 /pmc/articles/PMC8290130/ /pubmed/34295818 http://dx.doi.org/10.3389/fonc.2021.682859 Text en Copyright © 2021 Liu, Yang, Liu, Nie, Zhang, Lu, Pan, Wang and Luo https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Liu, Menghan
Yang, Lin
Liu, Xiaojun
Nie, Ziyuan
Zhang, Xiaoyan
Lu, Yaqiong
Pan, Yuxia
Wang, Xingzhe
Luo, Jianmin
HNRNPH1 Is a Novel Regulator Of Cellular Proliferation and Disease Progression in Chronic Myeloid Leukemia
title HNRNPH1 Is a Novel Regulator Of Cellular Proliferation and Disease Progression in Chronic Myeloid Leukemia
title_full HNRNPH1 Is a Novel Regulator Of Cellular Proliferation and Disease Progression in Chronic Myeloid Leukemia
title_fullStr HNRNPH1 Is a Novel Regulator Of Cellular Proliferation and Disease Progression in Chronic Myeloid Leukemia
title_full_unstemmed HNRNPH1 Is a Novel Regulator Of Cellular Proliferation and Disease Progression in Chronic Myeloid Leukemia
title_short HNRNPH1 Is a Novel Regulator Of Cellular Proliferation and Disease Progression in Chronic Myeloid Leukemia
title_sort hnrnph1 is a novel regulator of cellular proliferation and disease progression in chronic myeloid leukemia
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290130/
https://www.ncbi.nlm.nih.gov/pubmed/34295818
http://dx.doi.org/10.3389/fonc.2021.682859
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