MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to Chemoresistance
MicroRNAs (miRs) play an important role in tumorogenesis and chemoresistance in lymphoid malignancies. Comparing with reactive hyperplasia, miR181a was overexpressed in 130 patients with T-cell leukemia/lymphoma, including acute T-cell lymphoblastic leukemia (n = 32), T-cell lymphoblastic lymphoma (...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Hindawi Publishing Corporation
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575996/ https://www.ncbi.nlm.nih.gov/pubmed/26436088 http://dx.doi.org/10.1155/2015/197241 |
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author | Yan, Zi-Xun Zheng, Zhong Xue, Wen Zhao, Ming-Zhe Fei, Xiao-Chun Wu, Li-Li Huang, Li-Min Leboeuf, Christophe Janin, Anne Wang, Li Zhao, Wei-Li |
author_facet | Yan, Zi-Xun Zheng, Zhong Xue, Wen Zhao, Ming-Zhe Fei, Xiao-Chun Wu, Li-Li Huang, Li-Min Leboeuf, Christophe Janin, Anne Wang, Li Zhao, Wei-Li |
author_sort | Yan, Zi-Xun |
collection | PubMed |
description | MicroRNAs (miRs) play an important role in tumorogenesis and chemoresistance in lymphoid malignancies. Comparing with reactive hyperplasia, miR181a was overexpressed in 130 patients with T-cell leukemia/lymphoma, including acute T-cell lymphoblastic leukemia (n = 32), T-cell lymphoblastic lymphoma (n = 16), peripheral T-cell lymphoma, not otherwise specified (n = 45), anaplastic large cell lymphoma (n = 15), and angioimmunoblastic T-cell lymphoma (n = 22). Irrespective to histological subtypes, miR181a overexpression was associated with increased AKT phosphorylation. In vitro, ectopic expression of miR181a in HEK-293T cells significantly enhanced cell proliferation, activated AKT, and conferred cell resistance to doxorubicin. Meanwhile, miR181a expression was upregulated in Jurkat cells, along with AKT activation, during exposure to chemotherapeutic agents regularly applied to T-cell leukemia/lymphoma treatment, such as doxorubicin, cyclophosphamide, cytarabine, and cisplatin. Isogenic doxorubicin-resistant Jurkat and H9 cells were subsequently developed, which also presented with miR181a overexpression and cross-resistance to cyclophosphamide and cisplatin. Meanwhile, specific inhibition of miR181a enhanced Jurkat and H9 cell sensitivity to chemotherapeutic agents, further indicating that miR181a was involved in acquired chemoresistance. Collectively, miR181a functioned as a biomarker of T-cell leukemia/lymphoma through modulation of AKT pathway. Related to tumor cell chemoresistance, miR181a could be a potential therapeutic target in treating T-cell malignancies. |
format | Online Article Text |
id | pubmed-4575996 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-45759962015-10-04 MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to Chemoresistance Yan, Zi-Xun Zheng, Zhong Xue, Wen Zhao, Ming-Zhe Fei, Xiao-Chun Wu, Li-Li Huang, Li-Min Leboeuf, Christophe Janin, Anne Wang, Li Zhao, Wei-Li Biomed Res Int Research Article MicroRNAs (miRs) play an important role in tumorogenesis and chemoresistance in lymphoid malignancies. Comparing with reactive hyperplasia, miR181a was overexpressed in 130 patients with T-cell leukemia/lymphoma, including acute T-cell lymphoblastic leukemia (n = 32), T-cell lymphoblastic lymphoma (n = 16), peripheral T-cell lymphoma, not otherwise specified (n = 45), anaplastic large cell lymphoma (n = 15), and angioimmunoblastic T-cell lymphoma (n = 22). Irrespective to histological subtypes, miR181a overexpression was associated with increased AKT phosphorylation. In vitro, ectopic expression of miR181a in HEK-293T cells significantly enhanced cell proliferation, activated AKT, and conferred cell resistance to doxorubicin. Meanwhile, miR181a expression was upregulated in Jurkat cells, along with AKT activation, during exposure to chemotherapeutic agents regularly applied to T-cell leukemia/lymphoma treatment, such as doxorubicin, cyclophosphamide, cytarabine, and cisplatin. Isogenic doxorubicin-resistant Jurkat and H9 cells were subsequently developed, which also presented with miR181a overexpression and cross-resistance to cyclophosphamide and cisplatin. Meanwhile, specific inhibition of miR181a enhanced Jurkat and H9 cell sensitivity to chemotherapeutic agents, further indicating that miR181a was involved in acquired chemoresistance. Collectively, miR181a functioned as a biomarker of T-cell leukemia/lymphoma through modulation of AKT pathway. Related to tumor cell chemoresistance, miR181a could be a potential therapeutic target in treating T-cell malignancies. Hindawi Publishing Corporation 2015 2015-09-07 /pmc/articles/PMC4575996/ /pubmed/26436088 http://dx.doi.org/10.1155/2015/197241 Text en Copyright © 2015 Zi-Xun Yan et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Yan, Zi-Xun Zheng, Zhong Xue, Wen Zhao, Ming-Zhe Fei, Xiao-Chun Wu, Li-Li Huang, Li-Min Leboeuf, Christophe Janin, Anne Wang, Li Zhao, Wei-Li MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to Chemoresistance |
title | MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to Chemoresistance |
title_full | MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to Chemoresistance |
title_fullStr | MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to Chemoresistance |
title_full_unstemmed | MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to Chemoresistance |
title_short | MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to Chemoresistance |
title_sort | microrna181a is overexpressed in t-cell leukemia/lymphoma and related to chemoresistance |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4575996/ https://www.ncbi.nlm.nih.gov/pubmed/26436088 http://dx.doi.org/10.1155/2015/197241 |
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