Musashi-2 Silencing Exerts Potent Activity against Acute Myeloid Leukemia and Enhances Chemosensitivity to Daunorubicin

doi:10.1371/journal.pone.0136484

科研成果详情

题名	Musashi-2 Silencing Exerts Potent Activity against Acute Myeloid Leukemia and Enhances Chemosensitivity to Daunorubicin
作者	Han, Yixiang1; Ye, Aifang1; Zhang, Yan 2,3; Cai, Zhimin1; Wang, Wei4; Sun, Lan4; Jiang, Songfu4; Wu, Jianbo1; Yu, Kang4; Zhang, Shenghui4
发表日期	2015-08-26
发表期刊	PLOS ONE 影响因子和分区
语种	英语
原始文献类型	Article
其他关键词	ACUTE LYMPHOBLASTIC-LEUKEMIA ; POOR-PROGNOSIS ; CELL-FATE ; ACTIVATION ; APOPTOSIS ; GROWTH ; MSI2 ; INHIBITION ; EXPRESSION ; INDUCTION
摘要	RNA-binding protein Musashi-2 (Msi2) is known to play a critical role in leukemogenesis and contributes to poor clinical prognosis in acute myeloid leukemia (AML). However, the effect of Msi2 silencing on treatment for AML still remains poorly understood. In this study, we used lentivirus-mediated RNA interference targeting Msi2 to investigate the resulting changes in cellular processes and the underlying mechanisms in AML cell lines as well as primary AML cells isolated from AML patients. We found that Msi2 was highly expressed in AML cells, and its depletion inhibited Ki-67 expression and resulted in decreased in vitro and in vivo proliferation. Msi2 silencing induced cell cycle arrest in G0/G1 phase, with decreased Cyclin D1 and increased p21 expression. Msi2 silencing induced apoptosis through down-regulation of Bcl-2 expression and up-regulation of Bax expression. Suppression of Akt, Erk1/2 and p38 phosphorylation also contributed to apoptosis mediated by Msi2 silencing. Finally, Msi2 silencing in AML cells also enhanced their chemosensitivity to daunorubicin. Conclusively, our data suggest that Msi2 is a promising target for gene therapy to optimize conventional chemotherapeutics in AML treatment.
资助项目	National Natural Science of Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81100355, 81172613, 81300430]; Zhejiang Provincial Natural Science Foundation of ChinaNatural Science Foundation of Zhejiang Province [LQ12H08002, Y2111000]
出版者	PUBLIC LIBRARY SCIENCE
出版地	SAN FRANCISCO
ISSN	1932-6203
卷号	10 期号:8 页码:e0136484.
DOI	10.1371/journal.pone.0136484
页数	15
WOS类目	Multidisciplinary Sciences
WOS研究方向	Science & Technology - Other Topics
WOS记录号	WOS:000360069400128
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	26308531
PMC记录号	PMC4550418
SCOPUSEID	2-s2.0-84943188467
通讯作者地址	[Zhang, Shenghui]Wenzhou Med Univ, Affiliated Hosp 1, Dept Hematol, Wenzhou 325015, Peoples R China.
Scopus学科分类	Multidisciplinary
引用统计	被引频次：23[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/18608
专题	附属第一医院_内科实验室附属第一医院_血液内科
通讯作者	Zhang, Shenghui
作者单位	1.Wenzhou Med Univ, Affiliated Hosp 1, Lab Internal Med, Wenzhou 325015, Peoples R China; 2.Fudan Univ, Shanghai Med Coll, Minist Educ, Key Lab Mol Med, Shanghai 200032, Peoples R China; 3.Fudan Univ, Shanghai Med Coll, Dept Biochem & Mol Biol, Shanghai 200032, Peoples R China; 4.Wenzhou Med Univ, Affiliated Hosp 1, Dept Hematol, Wenzhou 325015, Peoples R China
第一作者单位	附属第一医院_内科实验室
通讯作者单位	附属第一医院_血液内科
第一作者的第一单位	附属第一医院_内科实验室
推荐引用方式 GB/T 7714	Han, Yixiang,Ye, Aifang,Zhang, Yan,et al. Musashi-2 Silencing Exerts Potent Activity against Acute Myeloid Leukemia and Enhances Chemosensitivity to Daunorubicin[J]. PLOS ONE,2015,10(8):e0136484..
APA	Han, Yixiang., Ye, Aifang., Zhang, Yan., Cai, Zhimin., Wang, Wei., ... & Zhang, Shenghui. (2015). Musashi-2 Silencing Exerts Potent Activity against Acute Myeloid Leukemia and Enhances Chemosensitivity to Daunorubicin. PLOS ONE, 10(8), e0136484..
MLA	Han, Yixiang,et al."Musashi-2 Silencing Exerts Potent Activity against Acute Myeloid Leukemia and Enhances Chemosensitivity to Daunorubicin".PLOS ONE 10.8(2015):e0136484..