AntagomiR-19a Induced Better Responsiveness to Bortezomib in Myeloma Cell Lines

Objective: Multiple myeloma (MM) is the clonal proliferation of neoplastic plasma cells in the bone marrow. Although bortezomib (BTZ) is a crucial drug for the treatment of MM, drug resistance is a major problem. OncomiR-19a plays an oncogenic role in many cancers, including MM; however, the functio...

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Autores principales: Azam Kazemi, Saeid Abroun, Masoud Soleimani
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Publicado: Royan Institute (ACECR), Tehran 2021
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spelling oai:doaj.org-article:d0a174c47a674058bb15b47c9426b3fd2021-11-07T06:54:35ZAntagomiR-19a Induced Better Responsiveness to Bortezomib in Myeloma Cell Lines10.22074/cellj.2021.73022228-58062228-5814https://doaj.org/article/d0a174c47a674058bb15b47c9426b3fd2021-10-01T00:00:00Zhttps://celljournal.org/journal/article/fulltext/induced-anti-mir-19a-overcomes-drug-resistance-in-myeloma-cell-lines.pdfhttps://doaj.org/toc/2228-5806https://doaj.org/toc/2228-5814Objective: Multiple myeloma (MM) is the clonal proliferation of neoplastic plasma cells in the bone marrow. Although bortezomib (BTZ) is a crucial drug for the treatment of MM, drug resistance is a major problem. OncomiR-19a plays an oncogenic role in many cancers, including MM; however, the function of miR-19a in the pathogenesis of MM and drug resistance has not been completely identified. The present research aims to investigate the inhibition of miR-19a by an antagomir to determine BTZ responsiveness, and determine if miR-19a can be a prognostic biomarker for MM. Materials and Methods: In this experimental study, viability and apoptosis of myeloma cells were analysed by the colorimetric 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide (MTT) and Annexin V/propidium iodide (PI) flow cytometry assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was implemented to evaluate the expression levels of miR-19a, its targets SOCS3, STAT3, B-cell lymphoma 2 (BCL-2), PTEN and CDKN1A (antiapoptotic and cell cycle related genes) at the mRNA level. Results: miR-19a was downregulated and exacerbated in transfected cells treated with BTZ. The rate of apoptosis in the myeloma cells after BTZ treatment considerably increased, which indicated an increase in the mRNA of SOCS3, PTEN, BCL-2, and CDKN1. A decrease in STAT3 was also observed. Conclusion: OncomiR-19a, as a biomarker, may induce better responsiveness to BTZ in myeloma cell lines through its targets SOCS3, STAT3 and PTEN. In the future, this biomarker may provide new therapeutic targets for MM.Azam KazemiSaeid AbrounMasoud SoleimaniRoyan Institute (ACECR), Tehranarticleantagomir-19abortezomibmultiple myelomasocs3MedicineRScienceQENCell Journal, Vol 23, Iss 5, Pp 503-509 (2021)
institution DOAJ
collection DOAJ
language EN
topic antagomir-19a
bortezomib
multiple myeloma
socs3
Medicine
R
Science
Q
spellingShingle antagomir-19a
bortezomib
multiple myeloma
socs3
Medicine
R
Science
Q
Azam Kazemi
Saeid Abroun
Masoud Soleimani
AntagomiR-19a Induced Better Responsiveness to Bortezomib in Myeloma Cell Lines
description Objective: Multiple myeloma (MM) is the clonal proliferation of neoplastic plasma cells in the bone marrow. Although bortezomib (BTZ) is a crucial drug for the treatment of MM, drug resistance is a major problem. OncomiR-19a plays an oncogenic role in many cancers, including MM; however, the function of miR-19a in the pathogenesis of MM and drug resistance has not been completely identified. The present research aims to investigate the inhibition of miR-19a by an antagomir to determine BTZ responsiveness, and determine if miR-19a can be a prognostic biomarker for MM. Materials and Methods: In this experimental study, viability and apoptosis of myeloma cells were analysed by the colorimetric 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide (MTT) and Annexin V/propidium iodide (PI) flow cytometry assays. Quantitative real-time polymerase chain reaction (qRT-PCR) was implemented to evaluate the expression levels of miR-19a, its targets SOCS3, STAT3, B-cell lymphoma 2 (BCL-2), PTEN and CDKN1A (antiapoptotic and cell cycle related genes) at the mRNA level. Results: miR-19a was downregulated and exacerbated in transfected cells treated with BTZ. The rate of apoptosis in the myeloma cells after BTZ treatment considerably increased, which indicated an increase in the mRNA of SOCS3, PTEN, BCL-2, and CDKN1. A decrease in STAT3 was also observed. Conclusion: OncomiR-19a, as a biomarker, may induce better responsiveness to BTZ in myeloma cell lines through its targets SOCS3, STAT3 and PTEN. In the future, this biomarker may provide new therapeutic targets for MM.
format article
author Azam Kazemi
Saeid Abroun
Masoud Soleimani
author_facet Azam Kazemi
Saeid Abroun
Masoud Soleimani
author_sort Azam Kazemi
title AntagomiR-19a Induced Better Responsiveness to Bortezomib in Myeloma Cell Lines
title_short AntagomiR-19a Induced Better Responsiveness to Bortezomib in Myeloma Cell Lines
title_full AntagomiR-19a Induced Better Responsiveness to Bortezomib in Myeloma Cell Lines
title_fullStr AntagomiR-19a Induced Better Responsiveness to Bortezomib in Myeloma Cell Lines
title_full_unstemmed AntagomiR-19a Induced Better Responsiveness to Bortezomib in Myeloma Cell Lines
title_sort antagomir-19a induced better responsiveness to bortezomib in myeloma cell lines
publisher Royan Institute (ACECR), Tehran
publishDate 2021
url https://doaj.org/article/d0a174c47a674058bb15b47c9426b3fd
work_keys_str_mv AT azamkazemi antagomir19ainducedbetterresponsivenesstobortezomibinmyelomacelllines
AT saeidabroun antagomir19ainducedbetterresponsivenesstobortezomibinmyelomacelllines
AT masoudsoleimani antagomir19ainducedbetterresponsivenesstobortezomibinmyelomacelllines
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