Reversal of glucocorticoid resistance in Acute Lymphoblastic Leukemia cells by miR-145

Objective To analyze the expression levels of miR-145 in ALL children and their effects on the prognosis of ALL and to explore the mechanism of miR-145 in reversing the resistance of ALL cells to glucocorticoids. Methods A GEO database dataset was used to analyze the expression levels of miR-145 in...

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Main Authors: Sili Long, Danwei Ren, Fangfang Zhong, Yana Niu, Xiang Qin, Dan Mu, Wenjun Liu
Format: Article
Language:English
Published: PeerJ Inc. 2020-06-01
Series:PeerJ
Subjects:
Online Access:https://peerj.com/articles/9337.pdf
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author Sili Long
Danwei Ren
Fangfang Zhong
Yana Niu
Xiang Qin
Dan Mu
Wenjun Liu
author_facet Sili Long
Danwei Ren
Fangfang Zhong
Yana Niu
Xiang Qin
Dan Mu
Wenjun Liu
author_sort Sili Long
collection DOAJ
description Objective To analyze the expression levels of miR-145 in ALL children and their effects on the prognosis of ALL and to explore the mechanism of miR-145 in reversing the resistance of ALL cells to glucocorticoids. Methods A GEO database dataset was used to analyze the expression levels of miR-145 in ALL children. The association between miR-145 and childhood prognosis was analyzed by the TARGET database data. The expression levels of miR-145 in the glucocorticoid-resistant ALL cell line CEM-C1 were increased by lipofectamine 2000-mediated transfection. Cell proliferation inhibition experiments were performed to detect the effect of miR-145 on the response of CEM-C1 cell line to glucocorticoids. The expression levels of the apoptotic, autophagic and drug resistance-associated genes and proteins were detected by qPCR and western blot analysis. Results The expression levels of miR-145 were decreased in ALL patients (P < 0.001) and the prognosis of ALL in children with high miR-145 expression was significantly improved (P < 0.001). Increased miR-145 expression can improve the sensitivity of CEM-C1 cells to glucocorticoids. The expression levels of the proapoptotic and the anti-apoptotic genes Bax and Bcl-2 were increased and decreased, respectively, whereas the expression levels of the autophagicgenes Beclin 1 and LC were increased. In addition, the expression levels of the drug resistance gene MDR1 were decreased. Conclusion The expression levels of miR-145 in ALL children were decreased and they were associated with disease prognosis. The data indicated that miR-145 can reverse cell resistance by regulating apoptosis of CEM-C1 cells and autophagy.
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spelling doaj.art-708d861f0f514dc781cdca6a32a71dfb2023-12-03T11:20:46ZengPeerJ Inc.PeerJ2167-83592020-06-018e933710.7717/peerj.9337Reversal of glucocorticoid resistance in Acute Lymphoblastic Leukemia cells by miR-145Sili LongDanwei RenFangfang ZhongYana NiuXiang QinDan MuWenjun LiuObjective To analyze the expression levels of miR-145 in ALL children and their effects on the prognosis of ALL and to explore the mechanism of miR-145 in reversing the resistance of ALL cells to glucocorticoids. Methods A GEO database dataset was used to analyze the expression levels of miR-145 in ALL children. The association between miR-145 and childhood prognosis was analyzed by the TARGET database data. The expression levels of miR-145 in the glucocorticoid-resistant ALL cell line CEM-C1 were increased by lipofectamine 2000-mediated transfection. Cell proliferation inhibition experiments were performed to detect the effect of miR-145 on the response of CEM-C1 cell line to glucocorticoids. The expression levels of the apoptotic, autophagic and drug resistance-associated genes and proteins were detected by qPCR and western blot analysis. Results The expression levels of miR-145 were decreased in ALL patients (P < 0.001) and the prognosis of ALL in children with high miR-145 expression was significantly improved (P < 0.001). Increased miR-145 expression can improve the sensitivity of CEM-C1 cells to glucocorticoids. The expression levels of the proapoptotic and the anti-apoptotic genes Bax and Bcl-2 were increased and decreased, respectively, whereas the expression levels of the autophagicgenes Beclin 1 and LC were increased. In addition, the expression levels of the drug resistance gene MDR1 were decreased. Conclusion The expression levels of miR-145 in ALL children were decreased and they were associated with disease prognosis. The data indicated that miR-145 can reverse cell resistance by regulating apoptosis of CEM-C1 cells and autophagy.https://peerj.com/articles/9337.pdfAcute lymphoblastic leukemiamiR-145ChildrenGlucocorticoidDrug resistance
spellingShingle Sili Long
Danwei Ren
Fangfang Zhong
Yana Niu
Xiang Qin
Dan Mu
Wenjun Liu
Reversal of glucocorticoid resistance in Acute Lymphoblastic Leukemia cells by miR-145
PeerJ
Acute lymphoblastic leukemia
miR-145
Children
Glucocorticoid
Drug resistance
title Reversal of glucocorticoid resistance in Acute Lymphoblastic Leukemia cells by miR-145
title_full Reversal of glucocorticoid resistance in Acute Lymphoblastic Leukemia cells by miR-145
title_fullStr Reversal of glucocorticoid resistance in Acute Lymphoblastic Leukemia cells by miR-145
title_full_unstemmed Reversal of glucocorticoid resistance in Acute Lymphoblastic Leukemia cells by miR-145
title_short Reversal of glucocorticoid resistance in Acute Lymphoblastic Leukemia cells by miR-145
title_sort reversal of glucocorticoid resistance in acute lymphoblastic leukemia cells by mir 145
topic Acute lymphoblastic leukemia
miR-145
Children
Glucocorticoid
Drug resistance
url https://peerj.com/articles/9337.pdf
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