PTBP2-mediated alternative splicing of IRF9 controls tumor-associated monocyte/macrophage chemotaxis and repolarization in neuroblastoma progression

被引：26

作者：

Tang, Jue ^{[1
]}

He, Jing ^{[1
]}

Guo, Huiqin ^{[1
,2
]}

Lin, Huiran ^{[3
]}

Li, Meng ^{[1
]}

Yang, Tianyou ^{[1
]}

Wang, Hai-Yun ^{[1
]}

Li, Di ^{[1
]}

Liu, Jiabin ^{[1
]}

Li, Le ^{[1
]}

Xia, Huimin ^{[1
,5
]}

Zhuo, Zhenjian ^{[1
,4
,5
]}

Miao, Lei ^{[1
,5
]}

机构：

[1] Guangzhou Med Univ, Guangzhou Inst Pediat, Guangzhou Women & Childrens Med Ctr, Dept Pediat Surg, Guangzhou 510623, Guangdong, Peoples R China

[2] South China Univ Technol, Sch Med, Guangzhou 510623, Guangdong, Peoples R China

[3] Macau Univ Sci & Technol, Fac Med, Macau 999078, Peoples R China

[4] Peking Univ Shenzhen Grad Sch, Lab Anim Ctr, Sch Chem Biol & Biotechnol, Shenzhen 518055, Peoples R China

[5] Guangzhou Med Univ, Guangzhou Inst Pediat, Guangzhou Women & Childrens Med Ctr, Dept Pediat Surg, 9 Jinsui Rd, Guangzhou 510623, Guangdong, Peoples R China

来源：

RESEARCH | 2023年 / 2023卷

基金：

中国国家自然科学基金;

关键词：

neuroblastoma; tumor environment; tumor-associated macrophages; PTBP2; alternative splicing; I INTERFERON; BINDING PROTEINS; PHASE-I; MACROPHAGES; MONOCYTES; MECHANISMS; EXPRESSION; INHIBITION; INFECTION; RESPONSES;

D O I：

10.34133/research.0033

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The recurrence and metastasis of children with throactic neuroblastoma (NB) are also occurred after surgery, chemotherapy or radiotherapy. Strategies targeting the tumor microenvironment (TME) have been reported to improve survival, however, thorough investigations of monocytes and tumor-associated macrophages (TAMs) with specialized functions in NB are still lacking. Our data first demonstrated PTBP2 as a possible identifier in thoracic NB patients screened by proteomic profiling and that PTBP2 predicted good outcomes. Functional studies revealed that PTBP2 in NB cells induced the chemotactic activity and repolarization of tumor-associated monocytes and macrophages (M phi s), which in turn inhibited NB growth and dissemination. Mechanistically, PTBP2 prevents IRF9 alternative splicing, upregulates STAT1 to stimulate CCL5 and ISGF-dependent IFN-I secretion, to induce monocyte/M rectangle s chemotaxis and sustain monocytes in a proinflammatory phenotype. Our study defined a critical event of PTBP2-induced monocytes/M rectangle s in NB progression and revealed that RNA splicing occurred by PTBP2 benefits immune compartmentalization between NB cells and monocytes. This work revealed the pathological and biological role of PTBP2 in NB development and indicates that PTBP2-induced RNA splicing benefits immune compartmentalization and predicted a favorable prognosis in thoracic NB

引用

页数：54

共 45 条

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