Poster abstracts
Poster number 13 submitted by Ronghao Chen
The RNA-binding protein, PUM1, directly binds to and promotes the protein levels of PD-L1 in cancer cells
Ronghao Chen (Cancer Biology and Genetics, Ohio State University Medical Center), Swetha Rajasekaran (Cancer Biology and Genetics, Ohio State University Medical Center), Jing Wang (Cancer Biology and Genetics, Ohio State University Medical Center), Wayne Miles (Cancer Biology and Genetics, Ohio State University Medical Center)
Abstract:
Programmed death ligand 1 (PD-L1, CD274) is an essential immune checkpoint protein that binds to programmed death 1 (PD-1) on T-lymphocytes. This interaction, inhibits T-cell proliferation and activity, leading to tumor immunosuppression. High expression of PD-L1 contributes to immune evasion in cancer cells, which can be targeted using number of inhibitors. These therapies are effective and enable T-cell engagement of tumor cells. These approaches require PD-L1 protein production in tumor cells, however, the mechanisms that regulate these processes remain poorly defined. We find that PD-L1 RNA and protein levels are tightly regulated by the PUM1 RNA binding protein. Our data shows that PUM1 binds to a defined sequence in the 3’UTR of PD-L1 and that this interaction protects PD-L1 RNA from degradation. We find that shRNA-depletion or CRISPR-Cas9 deletion of PUM1 significantly decreases both the RNA and protein levels of PD-L1 in different cancer cells, including colon carcinoma, triple-negative breast cancer, and cervical carcinoma. Current studies are focused on the mechanism of PUM-regulation of PD-L1 and the testing of syngeneic mouse models. Our results identify a novel post-transcriptional regulatory mechanism that functions to regulate PD-L1 protein levels in tumors.
Keywords: PD-L1, PUM1, RNA-binding protein