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Exosomal mRNAs and lncRNAs involved in multiple myeloma resistance to bortezomib

The bone marrow microenvironment plays an essential role in multiple myeloma (MM) progression. We aimed to explore the alterations of levels of long noncoding RNAs and messenger RNAs (mRNAs), derived from exosomes in peripheral blood, in resistance to bortezomib (Btz) of MM patients. Peripheral bloo...

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Autores principales: Tang, Ju‐xian, Chen, Qi, Li, Qin, He, Yu‐han, Xiao, Duan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248034/
https://www.ncbi.nlm.nih.gov/pubmed/33372728
http://dx.doi.org/10.1002/cbin.11540
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author Tang, Ju‐xian
Chen, Qi
Li, Qin
He, Yu‐han
Xiao, Duan
author_facet Tang, Ju‐xian
Chen, Qi
Li, Qin
He, Yu‐han
Xiao, Duan
author_sort Tang, Ju‐xian
collection PubMed
description The bone marrow microenvironment plays an essential role in multiple myeloma (MM) progression. We aimed to explore the alterations of levels of long noncoding RNAs and messenger RNAs (mRNAs), derived from exosomes in peripheral blood, in resistance to bortezomib (Btz) of MM patients. Peripheral blood samples were collected from five Btz‐resistant and five Btz‐sensitive MM patients. Exosomes in patients' peripheral blood were enriched, and the profiles of long noncoding RNAs (lncRNAs) and mRNAs in exosomes were determined using deep sequencing. Bioinformatics analysis was performed to explore biological function. MTS was employed to determine the viability of Roswell Park Memorial Institute (RPMI) 8226 and LP‐1 cells incubated with exosomes derived from Btz‐resistant patients. Quantitative polymerase chain reaction (qPCR) was used to evaluate the levels of exosomal FFAR1, SP9, HIST1H2BG, and ITIH2. Incubation with Btz‐resistant patient‐derived exosomes significantly increased the viability of Btz‐treated RPMI 8226 and LP‐1 cells in a dose‐dependent manner. We identified 482 lncRNAs and 2099 mRNAs deregulated in exosomes of the Btz‐resistance group; and 78 mRNAs were enriched in DR‐related pathways, including mammalian target of rapamycin, platinum drug resistance, and the cAMP and phosphoinositide 3‐kinase–Akt signaling pathways. qPCR results verified the increases in FFAR1 and SP9 and decreases in HIST1H2BG and ITIH2 in Btz‐resistant patient‐derived exosomes. Moreover, exosomal FFAR1 and SP9 exhibited potential as independent prognostic indicators of survival of MM patients. Our study reveals significant dysregulation of exosomal RNA components in the Btz‐resistant group of MM patients as well as several mRNAs that may be used as biomarkers of prognosis of MM patients that are resistant to Btz.
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spelling pubmed-82480342021-07-02 Exosomal mRNAs and lncRNAs involved in multiple myeloma resistance to bortezomib Tang, Ju‐xian Chen, Qi Li, Qin He, Yu‐han Xiao, Duan Cell Biol Int Research Articles The bone marrow microenvironment plays an essential role in multiple myeloma (MM) progression. We aimed to explore the alterations of levels of long noncoding RNAs and messenger RNAs (mRNAs), derived from exosomes in peripheral blood, in resistance to bortezomib (Btz) of MM patients. Peripheral blood samples were collected from five Btz‐resistant and five Btz‐sensitive MM patients. Exosomes in patients' peripheral blood were enriched, and the profiles of long noncoding RNAs (lncRNAs) and mRNAs in exosomes were determined using deep sequencing. Bioinformatics analysis was performed to explore biological function. MTS was employed to determine the viability of Roswell Park Memorial Institute (RPMI) 8226 and LP‐1 cells incubated with exosomes derived from Btz‐resistant patients. Quantitative polymerase chain reaction (qPCR) was used to evaluate the levels of exosomal FFAR1, SP9, HIST1H2BG, and ITIH2. Incubation with Btz‐resistant patient‐derived exosomes significantly increased the viability of Btz‐treated RPMI 8226 and LP‐1 cells in a dose‐dependent manner. We identified 482 lncRNAs and 2099 mRNAs deregulated in exosomes of the Btz‐resistance group; and 78 mRNAs were enriched in DR‐related pathways, including mammalian target of rapamycin, platinum drug resistance, and the cAMP and phosphoinositide 3‐kinase–Akt signaling pathways. qPCR results verified the increases in FFAR1 and SP9 and decreases in HIST1H2BG and ITIH2 in Btz‐resistant patient‐derived exosomes. Moreover, exosomal FFAR1 and SP9 exhibited potential as independent prognostic indicators of survival of MM patients. Our study reveals significant dysregulation of exosomal RNA components in the Btz‐resistant group of MM patients as well as several mRNAs that may be used as biomarkers of prognosis of MM patients that are resistant to Btz. John Wiley and Sons Inc. 2021-01-15 2021-05 /pmc/articles/PMC8248034/ /pubmed/33372728 http://dx.doi.org/10.1002/cbin.11540 Text en © 2021 The Authors. Cell Biology International published by John Wiley & Sons Ltd on behalf of International Federation of Cell Biology https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research Articles
Tang, Ju‐xian
Chen, Qi
Li, Qin
He, Yu‐han
Xiao, Duan
Exosomal mRNAs and lncRNAs involved in multiple myeloma resistance to bortezomib
title Exosomal mRNAs and lncRNAs involved in multiple myeloma resistance to bortezomib
title_full Exosomal mRNAs and lncRNAs involved in multiple myeloma resistance to bortezomib
title_fullStr Exosomal mRNAs and lncRNAs involved in multiple myeloma resistance to bortezomib
title_full_unstemmed Exosomal mRNAs and lncRNAs involved in multiple myeloma resistance to bortezomib
title_short Exosomal mRNAs and lncRNAs involved in multiple myeloma resistance to bortezomib
title_sort exosomal mrnas and lncrnas involved in multiple myeloma resistance to bortezomib
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248034/
https://www.ncbi.nlm.nih.gov/pubmed/33372728
http://dx.doi.org/10.1002/cbin.11540
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