Summary
Published in Nature Communications (2017), this peer-reviewed study used 3D Petri Dish® micro-molds to form scaffold-free 3D microtissues. Full citation: Jiang, Runqiu, et al. The long noncoding RNA lnc-EGFR stimulates T-regulatory cells differentiation thus promoting hepatocellular carcinoma immune evasion
The long noncoding RNA lnc-EGFR stimulates T-regulatory cells differentiation thus promoting hepatocellular carcinoma immune evasion
Research Overview
Long noncoding RNAs are pivotal in T-helper cell development, but their roles in regulatory T cell (Treg) differentiation and function during hepatocellular carcinoma progression were little known. This study found that lnc-EGFR upregulation in Tregs correlated positively with tumor size and EGFR/Foxp3 expression and negatively with IFN-γ in patients and xenografted mice.
Lnc-EGFR stimulated Treg differentiation, suppressed cytotoxic T lymphocyte activity, and promoted HCC growth in an EGFR-dependent manner. Mechanistically, it binds EGFR and blocks its interaction with and ubiquitination by c-CBL, stabilizing EGFR and amplifying activation of the downstream AP-1/NF-AT1 axis, which in turn drives further EGFR expression — linking an immunosuppressive state to cancer via Treg differentiation.
Key Discoveries
- Lnc-EGFR in Tregs correlated with HCC tumor size and EGFR/Foxp3, inversely with IFN-γ
- Lnc-EGFR drove Treg differentiation, suppressed CTLs, and promoted HCC growth EGFR-dependently
- Binds EGFR to block c-CBL ubiquitination, stabilizing EGFR and activating AP-1/NF-AT1
