Exosome-derived circTRPS1 promotes malignant phenotype and CD8+T cell exhaustion in bladder cancer microenvironments

被引:110
作者
Yang, Chen [1 ,2 ,3 ]
Wu, Siqi [1 ,2 ]
Mou, Zezhong [1 ,2 ]
Zhou, Quan [1 ,2 ]
Dai, Xiyu [1 ,2 ]
Ou, Yuxi [1 ,2 ]
Chen, Xinan [1 ,2 ]
Chen, Yiling [1 ,2 ]
Xu, Chenyang [1 ,2 ]
Hu, Yun [1 ,2 ]
Zhang, Limin [1 ,2 ]
Zou, Lujia [1 ,2 ]
Jin, Shengming [4 ]
Hu, Jimeng [1 ,2 ]
Mao, Shanhua [1 ,2 ]
Jiang, Haowen [1 ,2 ,3 ]
机构
[1] Fudan Univ, Huashan Hosp, Dept Urol, Shanghai, Peoples R China
[2] Fudan Univ, Huashan Hosp, Fudan Inst Urol, Shanghai, Peoples R China
[3] Fudan Univ, Natl Clin Res Ctr Aging & Med, Shanghai, Peoples R China
[4] Fudan Univ, Dept Urol, Shanghai Canc Ctr, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
TUMOR MICROENVIRONMENT; GLUTAMINASE; INHIBITION; MICRORNAS; RNA;
D O I
10.1016/j.ymthe.2022.01.022
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Circular RNAs (circRNAs) play critical roles in different dis-eases. Exosomes are important intermediates of intercellular communication. While both have been widely reported in can-cers, exosome-derived circRNAs are rarely studied. In this work, we identified the differently expressed circRNAs in bladder cancer (BCa) tissue and exosomes through high-throughput sequencing. RNA pull-down, RNA immunoprecip-itation, and luciferase reporter assays were used to investigate the interactions between specific circRNAs, microRNAs (miR-NAs), and mRNAs. Wound-healing, Transwell, Cell Counting Kit-8 (CCK8), and colony-formation assays were used to study the biological roles in vitro. Metabolomics were used to explore the mechanism of how specific circRNAs influenced BCa cell behavior. Flow cytometry was used to study how specific circR-NAs affected the function of CD8+ T cells in tumor microenvi-ronments. We identified that exosome-derived hsa_-circ_0085361 (circTRPS1) was correlated with aggressive phenotypes of BCa cells via sponging miR-141-3p. Metabolo-mics and RNA sequencing (RNA-seq) identified GLS1-medi-ated glutamine metabolism was involved in circTRPS1-medi-ated alterations. Exosomes derived from circTRPS1 knocked down BCa cells, prevented CD8+ T cells from exhaustion, and repressed the malignant phenotype of BCa cells. In conclu-sion, exosome-derived circTRPS1 from BCa cells can modulate the intracellular reactive oxygen species (ROS) balance and CD8+ T cell exhaustion via the circTRPS1/miR141-3p/GLS1 axis. Our work may provide a potential biomarker and thera-peutic target for BCa.
引用
收藏
页码:1054 / 1070
页数:17
相关论文
共 46 条
  • [1] Functions of the exosome in rRNA, snoRNA and snRNA synthesis
    Allmang, C
    Kufel, J
    Chanfreau, G
    Mitchell, P
    Petfalski, E
    Tollervey, D
    [J]. EMBO JOURNAL, 1999, 18 (19) : 5399 - 5410
  • [2] Extracellular vesicles as a source for non-invasive biomarkers in bladder cancer progression
    Andreu, Zoraida
    Otta Oshiro, Renan
    Redruello, Alberto
    Lopez-Martin, Soraya
    Gutierrez-Vazquez, Cristina
    Morato, Esperanza
    Isabel Marina, Ana
    Olivier Gomez, Carlos
    Yanez-Mo, Maria
    [J]. EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2017, 98 : 70 - 79
  • [3] miRNA sponges: soaking up miRNAs for regulation of gene expression
    Bak, Rasmus O.
    Mikkelsen, Jacob Giehm
    [J]. WILEY INTERDISCIPLINARY REVIEWS-RNA, 2014, 5 (03) : 317 - 333
  • [4] Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression
    Chang, Chih-Hao
    Qiu, Jing
    O'Sullivan, David
    Buck, Michael D.
    Noguchi, Takuro
    Curtis, Jonathan D.
    Chen, Qiongyu
    Gindin, Mariel
    Gubin, Matthew M.
    van der Windt, Gerritje J. W.
    Tonc, Elena
    Schreiber, Robert D.
    Pearce, Edward J.
    Pearce, Erika L.
    [J]. CELL, 2015, 162 (06) : 1229 - 1241
  • [5] CHAUDHRI G, 1986, J IMMUNOL, V137, P2646
  • [6] The Warburg and Crabtree effects: On the origin of cancer cell energy metabolism and of yeast glucose repression
    Diaz-Ruiz, Rodrigo
    Rigoulet, Michel
    Devin, Anne
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 2011, 1807 (06): : 568 - 576
  • [7] Selective glutamine metabolism inhibition in tumor cells improves antitumor T lymphocyte activity in triple-negative breast cancer
    Edwards, Deanna N.
    Ngwa, Verra M.
    Raybuck, Ariel L.
    Wang, Shan
    Hwang, Yoonha
    Kim, Laura C.
    Cho, Sung Hoon
    Paik, Yeeun
    Wang, Qingfei
    Zhang, Siyuan
    Manning, H. Charles
    Rathmell, Jeffrey C.
    Cook, Rebecca S.
    Boothby, Mark R.
    Chen, Jin
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2021, 131 (04)
  • [8] Reactive Oxygen Species: Involvement in T Cell Signaling and Metabolism
    Franchina, Davide G.
    Dostert, Catherine
    Brenner, Dirk
    [J]. TRENDS IN IMMUNOLOGY, 2018, 39 (06) : 489 - 502
  • [9] The roles of exosomal circularRNAsin cancer
    Gao, Nan
    Shi, Fangzhou
    Song, Dandan
    Xuan, Wei
    [J]. IUBMB LIFE, 2020, 72 (09) : 1909 - 1919
  • [10] Gentner B, 2009, NAT METHODS, V6, P63, DOI [10.1038/NMETH.1277, 10.1038/nmeth.1277]