MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment

Rae Anna Wilson, Cristina Espinosa-Diez, Nathan Kanner, Namita Chatterjee, Rebecca Ruhl, Christina Hipfinger, Sunil J. Advani, Jie Li, Omar F. Khan, Aleksandra Franovic, Sara M. Weis, Sushil Kumar, Lisa Coussens, Daniel G. Anderson, Clark C. Chen, David A. Cheresh, Sudarshan Anand

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Rather than targeting tumour cells directly, elements of the tumour microenvironment can be modulated to sensitize tumours to the effects of therapy. Here we report a unique mechanism by which ectopic microRNA-103 can manipulate tumour-associated endothelial cells to enhance tumour cell death. Using gain-and-loss of function approaches, we show that miR-103 exacerbates DNA damage and inhibits angiogenesis in vitro and in vivo. Local, systemic or vascular-targeted delivery of miR-103 in tumour-bearing mice decreased angiogenesis and tumour growth. Mechanistically, miR-103 regulation of its target gene TREX1 in endothelial cells governs the secretion of pro-inflammatory cytokines into the tumour microenvironment. Our data suggest that this inflammatory milieu may potentiate tumour cell death by supporting immune activation and inducing tumour expression of Fas and TRAIL receptors. Our findings reveal miR-mediated crosstalk between vasculature and tumour cells that can be exploited to improve the efficacy of chemotherapy and radiation.

Original languageEnglish (US)
Article number13597
JournalNature Communications
Volume7
DOIs
StatePublished - Nov 25 2016

Fingerprint

Tumor Microenvironment
MicroRNAs
Tumors
tumors
Neoplasms
angiogenesis
Endothelial cells
Cell death
Cell Death
death
Endothelial Cells
TNF-Related Apoptosis-Inducing Ligand Receptors
CD95 Antigens
Bearings (structural)
Cells
secretions
Chemotherapy
DNA Damage
Blood Vessels
chemotherapy

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Wilson, R. A., Espinosa-Diez, C., Kanner, N., Chatterjee, N., Ruhl, R., Hipfinger, C., ... Anand, S. (2016). MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment. Nature Communications, 7, [13597]. https://doi.org/10.1038/ncomms13597

MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment. / Wilson, Rae Anna; Espinosa-Diez, Cristina; Kanner, Nathan; Chatterjee, Namita; Ruhl, Rebecca; Hipfinger, Christina; Advani, Sunil J.; Li, Jie; Khan, Omar F.; Franovic, Aleksandra; Weis, Sara M.; Kumar, Sushil; Coussens, Lisa; Anderson, Daniel G.; Chen, Clark C.; Cheresh, David A.; Anand, Sudarshan.

In: Nature Communications, Vol. 7, 13597, 25.11.2016.

Research output: Contribution to journalArticle

Wilson, RA, Espinosa-Diez, C, Kanner, N, Chatterjee, N, Ruhl, R, Hipfinger, C, Advani, SJ, Li, J, Khan, OF, Franovic, A, Weis, SM, Kumar, S, Coussens, L, Anderson, DG, Chen, CC, Cheresh, DA & Anand, S 2016, 'MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment', Nature Communications, vol. 7, 13597. https://doi.org/10.1038/ncomms13597
Wilson RA, Espinosa-Diez C, Kanner N, Chatterjee N, Ruhl R, Hipfinger C et al. MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment. Nature Communications. 2016 Nov 25;7. 13597. https://doi.org/10.1038/ncomms13597
Wilson, Rae Anna ; Espinosa-Diez, Cristina ; Kanner, Nathan ; Chatterjee, Namita ; Ruhl, Rebecca ; Hipfinger, Christina ; Advani, Sunil J. ; Li, Jie ; Khan, Omar F. ; Franovic, Aleksandra ; Weis, Sara M. ; Kumar, Sushil ; Coussens, Lisa ; Anderson, Daniel G. ; Chen, Clark C. ; Cheresh, David A. ; Anand, Sudarshan. / MicroRNA regulation of endothelial TREX1 reprograms the tumour microenvironment. In: Nature Communications. 2016 ; Vol. 7.
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