Upregulated SPAG6 correlates with increased STAT1 and is associated with reduced sensitivity of interferon-α response in BCR::ABL1 negative myeloproliferative neoplasms

作者全名："Ding, Li; Luo, Jie; Du, Juan; Zhao, Beibei; Luo, Jin; Pan, Shirui; Zhang, Linyi; Yan, Xinyu; Li, Junnan; Liu, Lin"

作者地址："[Ding, Li; Luo, Jie; Zhao, Beibei; Luo, Jin; Pan, Shirui; Zhang, Linyi; Yan, Xinyu; Li, Junnan; Liu, Lin] Chongqing Med Univ, Affiliated Hosp 1, Dept Hematol, Chongqing, Peoples R China; [Ding, Li; Du, Juan] Southwest Med Univ, Affiliated Hosp, Dept Hematol, Luzhou, Peoples R China; [Liu, Lin] Chongqing Med Univ, Affiliated Hosp 1, Dept Hematol, 1 Youyi Rd, Chongqing 400042, Peoples R China"

通信作者："Liu, L (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Hematol, 1 Youyi Rd, Chongqing 400042, Peoples R China."

来源：CANCER SCIENCE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001063991500001

JCR分区：Q1

影响因子：4.5

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：interferon-alpha; myeloproliferative neoplasm; signal transducer and activator of transcription 1; sperm-associated antigen 6

摘要："Sperm-associated antigen 6 (SPAG6) has been identified as an oncogene or tumor suppressor in various types of human cancer. However, the role of SPAG6 in BCR:: ABL1 negative myeloproliferative neoplasms (MPNs) remains unclear. Herein, we found that SPAG6 was upregulated at the mRNA level in primary MPN cells and MPN-derived leukemia cell lines. The SPAG6 protein was primarily located in the cytoplasm around the nucleus and positively correlated with beta-tubulin expression. In vitro, forced expression of SPAG6 increased cell clone formation and promoted G1 to S cell cycle progression. Downregulation of SPAG6 promoted apoptosis, reduced G1 to S phase transition, and impaired cell proliferation and cytokine release accompanied by downregulated signal transducer and activator of transcription 1 (STAT1) expression. Furthermore, the inhibitory effect of interferon-a (INF-a) on the primary MPN cells with high SPAG6 expression was decreased. Downregulation of SPAG6 enhanced STAT1 induction, thus enhancing the proapoptotic and cell cycle arrest effects of INF-alpha both in vitro and in vivo. Finally, a decrease in SPAG6 protein expression was noted when the STAT1 signaling was blocked. Chromatin immunoprecipitation assays indicated that STAT1 protein could bind to the SPAG6 promoter, while the dual-luciferase reporter assay indicated that STAT1 could promote the expression of SPAG6. Our results substantiate the relationship between upregulated SPAG6, increased STAT1, and reduced sensitivity to INF-a response in MPN."

基金机构："We are thankful to the Experimental Research Center of The First Affiliated Hospital of Chongqing Medical University (Chongqing, China) for the site and technical support.; Experimental Research Center of The First Affiliated Hospital of Chongqing Medical University"

基金资助正文："We are thankful to the Experimental Research Center of The First Affiliated Hospital of Chongqing Medical University (Chongqing, China) for the site and technical support."