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ELAVL1 regulates PD-L1 mRNA stability to disrupt the infiltration of CD4-positive T cells in prostate cancer.
Cai, Zhonglin; Zhai, Xiuxia; Xu, Jidong; Hong, Tianyu; Yang, Kuo; Min, Shasha; Du, Jianuo; Cai, Zhikang; Wang, Zhong; Shen, Ming; Wang, Di; Shen, Yanting.
Afiliación
  • Cai Z; Department of Urology, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China; Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
  • Zhai X; School of Nursing, Peking University, Beijing, China; Health Service Department of the Guard Bureau of the General Office of the Central Committee of the Communist Party of China, Beijing, China.
  • Xu J; Department of Urology, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China.
  • Hong T; Department of Urology, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China.
  • Yang K; Department of Urology, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China.
  • Min S; Department of Urology, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China.
  • Du J; Department of Urology, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China.
  • Cai Z; Department of Urology, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China. Electronic address: 32955997@qq.com.
  • Wang Z; Department of Urology, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China. Electronic address: zhongwang2000@sina.com.
  • Shen M; National Health Commission (NHC) Key Laboratory of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China. Electronic address: shenming711@163.com.
  • Wang D; Center for bioinformatics, National Infrastructures for Translational Medicine, Institute of Clinical Medicine and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: wangdi0001@foxmail.com.
  • Shen Y; Department of Urology, Gongli Hospital of Shanghai Pudong New Area, Shanghai, China. Electronic address: shenyanting798@126.com.
Neoplasia ; 57: 101049, 2024 Nov.
Article en En | MEDLINE | ID: mdl-39265220
ABSTRACT
Prostate cancer (PCa) currently ranks second in male tumor mortality. Targeting immune checkpoint in tumor as immunotherapy is a new direction for tumor treatment. However, targeting PD-1/PD-L1 and CTLA4 to treat PCa has poor immunotherapeutic efficacy because PCa is known as a cold tumor. Understanding the mechanism of immunosuppression in PCa can promote the use of immunotherapy to treat PCa. ELAVL1 is highly expressed in many tumors, participates in almost all tumor biological activities and is an oncogene. ELAVL1 is also involved in the development and differentiation of T and B lymphocytes. However, the relationship between ELAVL1 and tumor immunity has not yet been reported. In recent years, ELAVL1 has been shown to regulate downstream targets in an m6A -dependent manner. PD-L1 has been shown to have m6A sites in multiple tumors that are regulated by m6A. In this study, ELAVL1 was highly expressed in PCa, and PCa with high ELAVL1 expression is immunosuppressive. Knocking down ELAVL1 reduced PD-L1 expression in PCa. Moreover, PD-L1 was shown to have an m6A site, and its m6A level was upregulated in PCa. ELAVL1 interacts with PD-L1 mRNA and promotes PD-L1 RNA stability via m6A, ultimately inhibiting the infiltration of CD4-positive T cells. In addition, androgen receptor (AR) was shown to be regulated with ELAVL1, and knocking down AR could also affect the expression of PD-L1. Therefore, ELAVL1 can directly or indirectly regulate the expression of PD-L1, thereby affecting the infiltration of CD4-positive T cells in PCa and ultimately leading to immune suppression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Linfocitos T CD4-Positivos / Regulación Neoplásica de la Expresión Génica / Estabilidad del ARN / Antígeno B7-H1 / Proteína 1 Similar a ELAV Límite: Humans / Male Idioma: En Revista: Neoplasia Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Linfocitos T CD4-Positivos / Regulación Neoplásica de la Expresión Génica / Estabilidad del ARN / Antígeno B7-H1 / Proteína 1 Similar a ELAV Límite: Humans / Male Idioma: En Revista: Neoplasia Asunto de la revista: NEOPLASIAS Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos