SCIENCE@home

miR25/93 mediates hypoxia-induced immunosuppression by repressing cGAS

Min-Zu Wu,Wei-Chung Cheng,Su‐Feng Chen,S. Nieh,Carolyn O’Connor,Chia‐Lin Liu,Wen‐Wei Tsai,Cheng-Jang Wu,L. Martin,Yaoh-Shiang Lin,Kou-Juey Wu,Li-Fan Lu,J. I. Izpisúa Belmonte

Published 2017 in Nature Cell Biology

ABSTRACT

The mechanisms by which hypoxic tumours evade immunological pressure and anti-tumour immunity remain elusive. Here, we report that two hypoxia-responsive microRNAs, miR-25 and miR-93, are important for establishing an immunosuppressive tumour microenvironment by downregulating expression of the DNA sensor cGAS. Mechanistically, miR-25/93 targets NCOA3, an epigenetic factor that maintains basal levels of cGAS expression, leading to repression of cGAS during hypoxia. This allows hypoxic tumour cells to escape immunological responses induced by damage-associated molecular pattern molecules, specifically the release of mitochondrial DNA. Moreover, restoring cGAS expression results in an anti-tumour immune response. Clinically, decreased levels of cGAS are associated with poor prognosis for patients with breast cancer harbouring high levels of miR-25/93. Together, these data suggest that inactivation of the cGAS pathway plays a critical role in tumour progression, and reveal a direct link between hypoxia-responsive miRNAs and adaptive immune responses to the hypoxic tumour microenvironment, thus unveiling potential new therapeutic strategies.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-48 of 48 references · Page 1 of 1

CITED BY

Showing 1-100 of 126 citing papers · Page 1 of 2

12
Next