By Meghan Bialt-DeCelie ‘19

Cancer can thrive and spread because of its ability to inactivate immune cells and prevent the production of molecules that help in tumor recognition and suppression. Cyclic GMP-AMP synthase (cGAS) is a molecule that would typically be produced in order to signal an immune response in the presence of a tumor. Under the low oxygen microenvironment of a tumor, however, there is increased levels of microRNAs miR25 and miR93.

Researchers, led by Dr. Min-Zu Wu, investigated these microRNAs that control the tumor’s microenvironment because they eventually lead to a lowering of cGAS levels. MicroRNAs do not code for proteins like messenger RNA, but they can silence messenger RNA. However, miR25 and miR93 do not suppress cGAS directly; they target a different factor which directly regulates cGAS expression, NCOA3. Experiments using a mouse model revealed to researchers that by inhibiting the expression of miR25 and miR93, cGAS was not inhibited and tumor growth slowed down compared to normal mice. They tested miR25 and miR93 inhibition in nude mice and found that the mice did not show a decreases in tumor growth, indicating that the cGAS immune pathway is directly involved.

This new understanding of the cGAS pathway can be a therapeutic target for inhibiting tumor growth.  

References:

1. M. Wu, et al., miR-25/93 mediates hypoxia-induced immunosuppression by repressing cGAS. Nature Cell Biology 19, 1286–1296 (2017). doi: 10.1038/ncb3615
2. Image retrieved from: https://commons.wikimedia.org/wiki/File:Bantam_microRNA_secondary_structure.png