Regulation of STAT5 phosphorylation and interaction with SHP1 by lnc-AC004893, a long non-coding RNA overexpressed in myeloproliferative neoplasms

doi:10.1080/16078454.2024.2375045

科研成果详情

题名	Regulation of STAT5 phosphorylation and interaction with SHP1 by lnc-AC004893, a long non-coding RNA overexpressed in myeloproliferative neoplasms
作者	Yang, Junjun1,2; Ruan, Jichen3; Zhou, Bin 4; Ye, Sisi 4; Gao, Shenmeng4; Zheng, Xiaoqun1,2,5
发表日期	2024-12-31
发表期刊	HEMATOLOGY 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Myeloproliferative neoplasms long noncoding RNAs STAT5 SHP1
其他关键词	ACTIVATION ; EXPRESSION ; LEUKEMIA ; IDENTIFICATION ; JAK2-STAT5 ; INHIBITOR ; KINASE
摘要	ObjectivesConstitutive activation of Janus kinase 2 (JAK2)/signal transducer and activator of transcription (STAT) signaling pathway is central to the pathogenesis of myeloproliferative neoplasms (MPNs). Long noncoding RNAs (lncRNAs) regulate diverse biological processes. However, the role of lncRNAs in MPN pathogenesis is not well studied.MethodsThe expression of lnc-AC004893 in MPN patients was measured by quantitative real-time PCR (qRT-PCR). Gene-specific short hairpin RNAs (shRNAs) were designed to inhibit the expression of lnc-AC004893, and western blot was performed to explore the role of lnc-AC004893 via regulating the JAK2/STAT5 signaling pathway. Furthermore, co-IP was performed to determine the binding ability of lnc-AC004893 and STAT5 protein. Finally, the BaF3-JAK2V617F-transplanted mouse model was used to assess the biological role of lnc-ac004893 in vivo.ResultsWe report that lnc-AC004893, a poorly conserved pseudogene-209, is substantially upregulated in MPN cells compared with normal controls (NCs). Knockdown of lnc-AC004893 by specific shRNAs suppressed cell proliferation and decreased colony formation. Furthermore, the knockdown of lnc-AC004893 reduced the expression of p-STAT5 but not total STAT5 in HEL and murine IL-3-dependent Ba/F3 cells, which present constitutive and inducible activation of JAK2/STAT5 signaling. In addition, inhibition of murine lnc-ac004893 attenuated BaF3-JAK2V617F-transplanted phenotypes and extended the overall survival. Mechanistically, knockdown of lnc-AC004893 enhanced the binding ability of STAT5 and protein tyrosine phosphatase SHP1. Furthermore, knockdown of lnc-AC004893 decreased STAT5-lnc-AC004893 interaction but not SHP1-lnc-AC004893 interaction.ConclusionLnc-AC004893 regulates STAT5 phosphorylation by affecting the interaction of STAT5 and SHP1. Lnc-AC004893 might be a potential therapeutic target for MPN patients.
资助项目	Natural Science Foundation of Zhejiang Province [LY19H080003]
出版者	TAYLOR & FRANCIS LTD
ISSN	1024-5332
EISSN	1607-8454
卷号	29 期号:1
DOI	10.1080/16078454.2024.2375045
页数	10
WOS类目	Hematology
WOS研究方向	Hematology
WOS记录号	WOS:001268763200001
收录类别	SCIE ; SCOPUS ; PUBMED
URL	查看原文
PubMed ID	39012197
SCOPUSEID	2-s2.0-85198639571
通讯作者地址	[Zheng, Xiaoqun]Wenzhou Med Univ, Affiliated Hosp 2, Dept Lab Med, Wenzhou, Peoples R China. ; [Zheng, Xiaoqun]Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou, Peoples R China. ; [Gao, Shenmeng]Wenzhou Med Univ, Affiliated Hosp 1, Med Res Ctr, Wenzhou, Peoples R China. ; [Zheng, Xiaoqun]Wenzhou Med Univ, Sch Lab Med & Life Sci, Wenzhou, Peoples R China.
Scopus学科分类	Hematology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/216823
专题	附属第二医院检验医学院（生命科学学院、生物学实验教学中心）附属第一医院第二临床医学院、附属第二医院、育英儿童医院附属第一医院_心血管内科附属第二医院_检验科附属第二医院_血液内科
通讯作者	Gao, Shenmeng; Zheng, Xiaoqun
作者单位	1.Wenzhou Med Univ, Affiliated Hosp 2, Dept Lab Med, Wenzhou, Peoples R China; 2.Wenzhou Med Univ, Yuying Childrens Hosp, Wenzhou, Peoples R China; 3.Wenzhou Med Univ, Affiliated Hosp 2, Dept Hematol, Wenzhou, Peoples R China; 4.Wenzhou Med Univ, Affiliated Hosp 1, Med Res Ctr, Wenzhou, Peoples R China; 5.Wenzhou Med Univ, Sch Lab Med & Life Sci, Wenzhou, Peoples R China
第一作者单位	附属第二医院; 第二临床医学院，附属第二医院、育英儿童医院; 检验科
通讯作者单位	附属第二医院; 第二临床医学院，附属第二医院、育英儿童医院; 检验科; 附属第一医院; 心血管内科; 检验医学院（生命科学学院、生物学实验教学中心）
第一作者的第一单位	附属第二医院
推荐引用方式 GB/T 7714	Yang, Junjun,Ruan, Jichen,Zhou, Bin,et al. Regulation of STAT5 phosphorylation and interaction with SHP1 by lnc-AC004893, a long non-coding RNA overexpressed in myeloproliferative neoplasms[J]. HEMATOLOGY,2024,29(1).
APA	Yang, Junjun, Ruan, Jichen, Zhou, Bin, Ye, Sisi, Gao, Shenmeng, & Zheng, Xiaoqun. (2024). Regulation of STAT5 phosphorylation and interaction with SHP1 by lnc-AC004893, a long non-coding RNA overexpressed in myeloproliferative neoplasms. HEMATOLOGY, 29(1).
MLA	Yang, Junjun,et al."Regulation of STAT5 phosphorylation and interaction with SHP1 by lnc-AC004893, a long non-coding RNA overexpressed in myeloproliferative neoplasms".HEMATOLOGY 29.1(2024).