Global identification of circular RNAs in imatinib (IM) resistance of chronic myeloid leukemia (CML) by modulating signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1

Abstract Imatinib (IM), targeting of BCR-ABL1 tyrosine kinase, is currently one of the first-line choices in the treatment of chronic myeloid leukemia (CML). This study aims to explore the molecular mechanisms underlying IM resistance in CML treatment. 108 CML patients were recruited and grouped acc...

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Autores principales:	Yao-hua Lu, Zhong-yi Huang
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Chronic myeloid leukemia Circular RNAs ABL1 Imatinib resistance miRNA Therapeutics. Pharmacology RM1-950 Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/2bf2ae6269f5407888192d9309895b93
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spelling	oai:doaj.org-article:2bf2ae6269f5407888192d9309895b932021-11-21T12:08:11ZGlobal identification of circular RNAs in imatinib (IM) resistance of chronic myeloid leukemia (CML) by modulating signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL110.1186/s10020-021-00395-z1076-15511528-3658https://doaj.org/article/2bf2ae6269f5407888192d9309895b932021-11-01T00:00:00Zhttps://doi.org/10.1186/s10020-021-00395-zhttps://doaj.org/toc/1076-1551https://doaj.org/toc/1528-3658Abstract Imatinib (IM), targeting of BCR-ABL1 tyrosine kinase, is currently one of the first-line choices in the treatment of chronic myeloid leukemia (CML). This study aims to explore the molecular mechanisms underlying IM resistance in CML treatment. 108 CML patients were recruited and grouped according to their sensitivity to IM as the responder group (N = 66) and the non-responder group (N = 42). Real-time quantitative PCR (RT-qPCR) was performed to evaluate the expression of candidate circular RNAs (circRNAs), microRNA (miRNAs) and messenger RNA (mRNAs). No significant difference was noted regarding demographic and clinicopathological characteristics between the responder group and the non-responder group. The expression of circ_0080145, circ_0051886 and ABL1 mRNA was significantly increased, while the expression of miR-203 and miR-637 was decreased in the non-responder group as compared with the responders. By using in-silicon analysis, it was predicted that circ_0080145 and circ_0051886 targeted miR-203 and miR-637 respectively, and ABL1 was found to be shared direct target gene of miR-203 and miR-637. Ectopic over-expression of circ_0080145 and circ_0051886 respectively reduced the expression of miR-203 and miR-637. The expression of ABL1 mRNA/protein was most upregulated in culture cells co-transfected with circ_0080145 and circ_0051886 as compared with those cells individually transfected. This study established the signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1. The deregulation of circ_0080145 and circ_0051886 is, at least partially, responsible for the development of IM chemoresistance in CML by regulating expression of ABL1 via modulating expression of miR-203 and miR-637.Yao-hua LuZhong-yi HuangBMCarticleChronic myeloid leukemiaCircular RNAsABL1Imatinib resistancemiRNATherapeutics. PharmacologyRM1-950BiochemistryQD415-436ENMolecular Medicine, Vol 27, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Chronic myeloid leukemia Circular RNAs ABL1 Imatinib resistance miRNA Therapeutics. Pharmacology RM1-950 Biochemistry QD415-436
spellingShingle	Chronic myeloid leukemia Circular RNAs ABL1 Imatinib resistance miRNA Therapeutics. Pharmacology RM1-950 Biochemistry QD415-436 Yao-hua Lu Zhong-yi Huang Global identification of circular RNAs in imatinib (IM) resistance of chronic myeloid leukemia (CML) by modulating signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1
description	Abstract Imatinib (IM), targeting of BCR-ABL1 tyrosine kinase, is currently one of the first-line choices in the treatment of chronic myeloid leukemia (CML). This study aims to explore the molecular mechanisms underlying IM resistance in CML treatment. 108 CML patients were recruited and grouped according to their sensitivity to IM as the responder group (N = 66) and the non-responder group (N = 42). Real-time quantitative PCR (RT-qPCR) was performed to evaluate the expression of candidate circular RNAs (circRNAs), microRNA (miRNAs) and messenger RNA (mRNAs). No significant difference was noted regarding demographic and clinicopathological characteristics between the responder group and the non-responder group. The expression of circ_0080145, circ_0051886 and ABL1 mRNA was significantly increased, while the expression of miR-203 and miR-637 was decreased in the non-responder group as compared with the responders. By using in-silicon analysis, it was predicted that circ_0080145 and circ_0051886 targeted miR-203 and miR-637 respectively, and ABL1 was found to be shared direct target gene of miR-203 and miR-637. Ectopic over-expression of circ_0080145 and circ_0051886 respectively reduced the expression of miR-203 and miR-637. The expression of ABL1 mRNA/protein was most upregulated in culture cells co-transfected with circ_0080145 and circ_0051886 as compared with those cells individually transfected. This study established the signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1. The deregulation of circ_0080145 and circ_0051886 is, at least partially, responsible for the development of IM chemoresistance in CML by regulating expression of ABL1 via modulating expression of miR-203 and miR-637.
format	article
author	Yao-hua Lu Zhong-yi Huang
author_facet	Yao-hua Lu Zhong-yi Huang
author_sort	Yao-hua Lu
title	Global identification of circular RNAs in imatinib (IM) resistance of chronic myeloid leukemia (CML) by modulating signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1
title_short	Global identification of circular RNAs in imatinib (IM) resistance of chronic myeloid leukemia (CML) by modulating signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1
title_full	Global identification of circular RNAs in imatinib (IM) resistance of chronic myeloid leukemia (CML) by modulating signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1
title_fullStr	Global identification of circular RNAs in imatinib (IM) resistance of chronic myeloid leukemia (CML) by modulating signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1
title_full_unstemmed	Global identification of circular RNAs in imatinib (IM) resistance of chronic myeloid leukemia (CML) by modulating signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1
title_sort	global identification of circular rnas in imatinib (im) resistance of chronic myeloid leukemia (cml) by modulating signaling pathways of circ_0080145/mir-203/abl1 and circ 0051886/mir-637/abl1
publisher	BMC
publishDate	2021
url	https://doaj.org/article/2bf2ae6269f5407888192d9309895b93
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_version_	1718419175028817920

Global identification of circular RNAs in imatinib (IM) resistance of chronic myeloid leukemia (CML) by modulating signaling pathways of circ_0080145/miR-203/ABL1 and circ 0051886/miR-637/ABL1

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