MiRNA-495 regulates proliferation and apoptosis of acute myeloid leukemia cells with MLL gene rearrangement by targeting STYX

Objective To investigate the effect of miRNA-495 on the proliferation and apoptosis of acute myeloid leukemia (AML) cells with mixed lineage leukemia (MLL) gene rearrangement. Methods Ten patients diagnosed with AML with MLL-AF9 fusion gene positive (6 males, 4 females, mean age of 39.37±2.71 years)...

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Autores principales:	YANG Rui, NING Jing, JING Lijuan, WANG Hainan, CUI Lijuan
Formato:	article
Lenguaje:	ZH
Publicado:	Editorial Office of Journal of Third Military Medical University 2021
Materias:	acute myeloid leukemia mll-af9 mirna-495 serine/threonine/tyrosine interacting protein cell proliferation Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/b2a3405a20e6413a88253e40053d99e8
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spelling	oai:doaj.org-article:b2a3405a20e6413a88253e40053d99e82021-11-28T10:39:36ZMiRNA-495 regulates proliferation and apoptosis of acute myeloid leukemia cells with MLL gene rearrangement by targeting STYX10.16016/j.1000-5404.2021050911000-5404https://doaj.org/article/b2a3405a20e6413a88253e40053d99e82021-11-01T00:00:00Zhttp://aammt.tmmu.edu.cn/Upload/rhtml/202105091.htmhttps://doaj.org/toc/1000-5404Objective To investigate the effect of miRNA-495 on the proliferation and apoptosis of acute myeloid leukemia (AML) cells with mixed lineage leukemia (MLL) gene rearrangement. Methods Ten patients diagnosed with AML with MLL-AF9 fusion gene positive (6 males, 4 females, mean age of 39.37±2.71 years), and 10 cases of AML (5 males, 5 females, mean age of 41.12±1.92 years) admitted in our hospital from August 2017 to May 2019 were enrolled in this study, and another 10 patients (6 males, 4 females, mean age of 42.31±3.21 years) who attended the surgical outpatient department during the same period were also collected as the control. THP-1 cells (containing MLL-AF9 fusion gene) were divided into miRNA-495 and control groups based on transfection with miRNA-495 or not, and the expression of miRNA-495 in each group was detected by RT-qPCR; CCK-8 assay was used to determine the proliferation of transfected THP-1 cells in each group; RT-qPCR and Western blotting were performed to measure the expression of proliferation-related factors (Ki-67 and PCNA) and apoptosis-related factors (Bcl-2, Bax and Caspase-3). The target genes of miRNA-495 were predicted by TargetScan and then verified by dual-luciferase reporter assay. Finally, RT-qPCR and Western blotting were adopted to detect the expression of serine/threonine/tyrosine interacting protein (STYX) in groups as follows: miRNA-495 group, control group, STYX group (transfected with STYX) and miRNA-495+STYX group (transfected with miRNA-495 and STYX). Results MiRNA-495 expression was down-regulated in AML patients with MLL-AF9 fusion gene, with relative expression of 0.25±0.08 (95%CI=-0.86~-0.65, P < 0.001); miRNA-495 inhibited cell proliferation (P < 0.001) and induced apoptosis of THP-1 cells, and it targetedly bound to STYX (P < 0.001). In addition, STYX overexpression reversed the effects of miRNA-495 on THP-1 cell proliferation and apoptosis. Conclusion MiRNA-495 regulates the proliferation and apoptosis of AML cells with MLL gene rearrangement by targeting STYX.YANG RuiNING JingJING LijuanWANG HainanCUI LijuanEditorial Office of Journal of Third Military Medical Universityarticleacute myeloid leukemiamll-af9mirna-495serine/threonine/tyrosine interacting proteincell proliferationMedicine (General)R5-920ZHDi-san junyi daxue xuebao, Vol 43, Iss 22, Pp 2407-2413 (2021)
institution	DOAJ
collection	DOAJ
language	ZH
topic	acute myeloid leukemia mll-af9 mirna-495 serine/threonine/tyrosine interacting protein cell proliferation Medicine (General) R5-920
spellingShingle	acute myeloid leukemia mll-af9 mirna-495 serine/threonine/tyrosine interacting protein cell proliferation Medicine (General) R5-920 YANG Rui NING Jing JING Lijuan WANG Hainan CUI Lijuan MiRNA-495 regulates proliferation and apoptosis of acute myeloid leukemia cells with MLL gene rearrangement by targeting STYX
description	Objective To investigate the effect of miRNA-495 on the proliferation and apoptosis of acute myeloid leukemia (AML) cells with mixed lineage leukemia (MLL) gene rearrangement. Methods Ten patients diagnosed with AML with MLL-AF9 fusion gene positive (6 males, 4 females, mean age of 39.37±2.71 years), and 10 cases of AML (5 males, 5 females, mean age of 41.12±1.92 years) admitted in our hospital from August 2017 to May 2019 were enrolled in this study, and another 10 patients (6 males, 4 females, mean age of 42.31±3.21 years) who attended the surgical outpatient department during the same period were also collected as the control. THP-1 cells (containing MLL-AF9 fusion gene) were divided into miRNA-495 and control groups based on transfection with miRNA-495 or not, and the expression of miRNA-495 in each group was detected by RT-qPCR; CCK-8 assay was used to determine the proliferation of transfected THP-1 cells in each group; RT-qPCR and Western blotting were performed to measure the expression of proliferation-related factors (Ki-67 and PCNA) and apoptosis-related factors (Bcl-2, Bax and Caspase-3). The target genes of miRNA-495 were predicted by TargetScan and then verified by dual-luciferase reporter assay. Finally, RT-qPCR and Western blotting were adopted to detect the expression of serine/threonine/tyrosine interacting protein (STYX) in groups as follows: miRNA-495 group, control group, STYX group (transfected with STYX) and miRNA-495+STYX group (transfected with miRNA-495 and STYX). Results MiRNA-495 expression was down-regulated in AML patients with MLL-AF9 fusion gene, with relative expression of 0.25±0.08 (95%CI=-0.86~-0.65, P < 0.001); miRNA-495 inhibited cell proliferation (P < 0.001) and induced apoptosis of THP-1 cells, and it targetedly bound to STYX (P < 0.001). In addition, STYX overexpression reversed the effects of miRNA-495 on THP-1 cell proliferation and apoptosis. Conclusion MiRNA-495 regulates the proliferation and apoptosis of AML cells with MLL gene rearrangement by targeting STYX.
format	article
author	YANG Rui NING Jing JING Lijuan WANG Hainan CUI Lijuan
author_facet	YANG Rui NING Jing JING Lijuan WANG Hainan CUI Lijuan
author_sort	YANG Rui
title	MiRNA-495 regulates proliferation and apoptosis of acute myeloid leukemia cells with MLL gene rearrangement by targeting STYX
title_short	MiRNA-495 regulates proliferation and apoptosis of acute myeloid leukemia cells with MLL gene rearrangement by targeting STYX
title_full	MiRNA-495 regulates proliferation and apoptosis of acute myeloid leukemia cells with MLL gene rearrangement by targeting STYX
title_fullStr	MiRNA-495 regulates proliferation and apoptosis of acute myeloid leukemia cells with MLL gene rearrangement by targeting STYX
title_full_unstemmed	MiRNA-495 regulates proliferation and apoptosis of acute myeloid leukemia cells with MLL gene rearrangement by targeting STYX
title_sort	mirna-495 regulates proliferation and apoptosis of acute myeloid leukemia cells with mll gene rearrangement by targeting styx
publisher	Editorial Office of Journal of Third Military Medical University
publishDate	2021
url	https://doaj.org/article/b2a3405a20e6413a88253e40053d99e8
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MiRNA-495 regulates proliferation and apoptosis of acute myeloid leukemia cells with MLL gene rearrangement by targeting STYX

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