WDR54 exerts oncogenic roles in T-cell acute lymphoblastic leukemia

作者全名："Li, Huan; Zhang, Danlan; Fu, Qiuxia; Wang, Shang; Zhang, Xin; Lin, Zhixian; Wang, Zhongyuan; Song, Jiaxing; Su, Zijie; Xue, Vivian Weiwen; Liu, Shanshan; Chen, Yun; Zhou, Liang; Zhao, Na; Lu, Desheng"

作者地址："[Li, Huan; Zhang, Danlan; Fu, Qiuxia; Zhang, Xin; Lin, Zhixian; Wang, Zhongyuan; Song, Jiaxing; Su, Zijie; Xue, Vivian Weiwen; Liu, Shanshan; Zhou, Liang; Lu, Desheng] Shenzhen Univ, Med Sch, Dept Pharmacol, Guangdong Prov Key Lab Reg Immun & Dis,Int Canc Ct, Shenzhen, Peoples R China; [Wang, Shang] Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, Chongqing, Peoples R China; [Chen, Yun] Nanjing Med Univ, Gusu Sch, Dept Immunol, Key Lab Human Funct Genom Jiangsu Prov, Nanjing, Peoples R China; [Zhao, Na] Univ Sci & Technol China, Affiliated Hosp 1, USTC, Dept Hematol,Div Life Sci & Med, Hefei, Peoples R China; [Lu, Desheng] Shenzhen Univ, Med Sch, Dept Pharmacol, Guangdong Prov Key Lab Reg Immun & Dis,Int Canc Ct, Shenzhen 518060, Guangdong, Peoples R China; [Zhao, Na] Univ Sci & Technol China, Affiliated Hosp 1, USTC, Dept Hematol,Div Life Sci & Med, Hefei 230001, Peoples R China"

通信作者："Lu, DS (通讯作者)，Shenzhen Univ, Med Sch, Dept Pharmacol, Guangdong Prov Key Lab Reg Immun & Dis,Int Canc Ct, Shenzhen 518060, Guangdong, Peoples R China.; Zhao, N (通讯作者)，Univ Sci & Technol China, Affiliated Hosp 1, USTC, Dept Hematol,Div Life Sci & Med, Hefei 230001, Peoples R China."

来源：CANCER SCIENCE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001007031800001

JCR分区：Q1

影响因子：4.5

年份：2023

卷号：114

期号：8

开始页：3318

结束页：3329

文献类型：Article

关键词：high mRNA and protein expression; leukemogenesis; proliferation and apoptosis related cell signal pathways; T-ALL; WDR54

摘要："WDR54 has been recently identified as a novel oncogene in colorectal and bladder cancers. However, the expression and function of WDR54 in T-cell acute lymphoblastic leukemia (T-ALL) were not reported. In this study, we investigated the expression of WDR54 in T-ALL, as well as its function in T-ALL pathogenesis using cell lines and T-ALL xenograft. Bioinformatics analysis indicated high mRNA expression of WDR54 in T-ALL. We further confirmed that the expression of WDR54 was significantly elevated in T-ALL. Depletion of WDR54 dramatically inhibited cell viability and induced apoptosis and cell cycle arrest at S phase in T-ALL cells in vitro. Moreover, knockdown of WDR54 impeded the process of leukemogenesis in a Jurkat xenograft model in vivo. Mechanistically, the expression of PDPK1, phospho-AKT (p-AKT), total AKT, phospho-ERK (p-ERK), Bcl-2 and Bcl-xL were downregulated, while cleaved caspase-3 and cleaved caspase-9 were upregulated in T-ALL cells with WDR54 knockdown. Additionally, RNA-seq analysis indicated that WDR54 might regulate the expression of some oncogenic genes involved in multiple signaling pathways. Taken together, these findings suggest that WDR54 may be involved in the pathogenesis of T-ALL and serve as a potential therapeutic target for the treatment of T-ALL."

基金机构：Anhui Natural Science Foundation [2108085QH322]; National Natural Science Foundation of China [31970739]; Shenzhen Natural Science Fund [20200826134656001]

基金资助正文："Anhui Natural Science Foundation, Grant/Award Number: 2108085QH322; National Natural Science Foundation of China, Grant/Award Number: 31970739; Shenzhen Natural Science Fund, Grant/Award Number: 20200826134656001"