Critical roles of the miR-17∼92 family in thymocyte development, leukemogenesis, and autoimmunity

被引：1

作者：

Liao, Kunyu ^{[1
]}

Chen, Pengda ^{[1
]}

Zhang, Mengdi ^{[3
,4
,5
]}

Wang, Jiazhen ^{[1
]}

Hatzihristidis, Teri ^{[6
]}

Lin, Xiaoxi ^{[3
,4
]}

Yang, Liang ^{[7
,8
]}

Yao, Nan ^{[7
,8
]}

Liu, Chenfeng ^{[1
]}

Hong, Yazhen ^{[1
]}

Li, Xia ^{[3
,4
]}

Liu, Hong ^{[5
,11
]}

Zuniga-Pflucker, Juan Carlos ^{[9
,10
]}

Love, Paul E. ^{[6
]}

Chen, Xiang ^{[5
,11
]}

Liu, Wen-Hsien ^{[1
]}

Zhao, Bin ^{[3
,4
,5
]}

Xiao, Changchun ^{[1
,2
,12
]}

机构：

[1] Xiamen Univ, Fac Med & Life Sci, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361102, Fujian, Peoples R China

[2] Scripps Res Inst, Dept Immunol & Microbiol, La Jolla, CA 92037 USA

[3] Cent South Univ, Xiangya Hosp 2, Natl Clin Res Ctr Metab Dis, Metab Syndrome Res Ctr,Key Lab Diabet Immunol,Mini, Changsha, Hunan, Peoples R China

[4] Cent South Univ, Xiangya Hosp 2, Dept Metab & Endocrinol, Changsha, Hunan, Peoples R China

[5] Furong Lab, Changsha, Peoples R China

[6] Eunice Kennedy Shriver Natl Inst Child Hlth & Huma, Sect Hematopoiesis & Lymphocyte Biol, NIH, Bethesda, MD USA

[7] Westlake Univ, Sch Life Sci, Westlake Lab Life Sci & Biomed, Key Lab Struct Biol Zhejiang Prov, Hangzhou, Zhejiang, Peoples R China

[8] Westlake Inst Adv Study, Inst Basic Med Sci, Hangzhou, Zhejiang, Peoples R China

[9] Univ Toronto, Dept Immunol, Toronto, ON, Canada

[10] Sunnybrook Res Inst, Toronto, ON, Canada

[11] Cent South Univ, Xiangya Hosp, Natl Engn Res Ctr Personalized Diagnost & Therapeu, Dept Dermatol,Hunan Engn Res Ctr Skin Hlth & Dis,H, Changsha, Hunan, Peoples R China

[12] Sanofi Inst Biomed Res, Suzhou 215123, Jiangsu, Peoples R China

来源：

CELL REPORTS | 2024年 / 43卷 / 06期

基金：

中国国家自然科学基金;

关键词：

T-CELL-DEVELOPMENT; C-MYC; GAMMA-DELTA; DIFFERENTIATION; EXPRESSION; MICRORNA; PROLIFERATION; PSORIASIS; NOTCH; SIGNALS;

D O I：

10.1016/j.celrep.2024.114261

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Thymocyte development requires precise control of PI3K-Akt signaling to promote proliferation and prevent leukemia and autoimmune disorders. Here, we show that ablating individual clusters of the miR-17 similar to 92 family has a negligible effect on thymocyte development, while deleting the entire family severely impairs thymocyte proliferation and reduces thymic cellularity, phenocopying genetic deletion of Dicer. Mechanistically, miR-17 similar to 92 expression is induced by Myc-mediated pre-T cell receptor (TCR) signaling, and miR-17 similar to 92 promotes thymocyte proliferation by suppressing the translation of Pten. Retroviral expression of miR-17 similar to 92 restores the proliferation and differentiation of Myc-deficient thymocytes. Conversely, partial deletion of the miR17 similar to 92 family significantly delays Myc-driven leukemogenesis. Intriguingly, thymocyte-specific transgenic miR-17 similar to 92 expression does not cause leukemia or lymphoma but instead aggravates skin inflammation, while ablation of the miR-17 similar to 92 family ameliorates skin inflammation. This study reveals intricate roles of the miR-17 similar to 92 family in balancing thymocyte development, leukemogenesis, and autoimmunity and identifies those microRNAs (miRNAs) as potential therapeutic targets for leukemia and autoimmune diseases.

引用

页数：24

共 70 条

[1] The role of Notch and IL-7 signaling in early thymocyte proliferation and differentiation [J].