Role of LncRNA UCA1 in OSCC CAFs: PD-L1 Upregulation and Tumor Progression.

OBJECTIVES

Characterize LncUCA1 expression in OSCC cancer-associated fibroblasts (CAFs), investigate immune regulation by high LncUCA1 CAFs, and assess their impact on tumor malignancy in vitro.

MATERIALS AND METHODS

Transcriptome sequencing identified upregulated genes in matched CAFs and normal fibroblasts (NFs) from OSCC patients. Clinical outcomes were evaluated in 21 OSCC patients. LncUCA1's effect on PD-L1 expression in CAFs was assessed by flow sorting and qRT-PCR. Co-culture experiments evaluated CAFs' impact on CD8 T cell proliferation and immunosuppression. Matrigel contraction and CCK8 assays explored CAFs' matrix contraction and proliferation. Direct co-culture analyzed CAFs' effect on OSCC proliferation. Transwell assays examined CAFs' impact on tumor cell migration and invasion.

RESULTS

LncUCA1 was significantly upregulated in CAFs compared to NFs. Higher LncUCA1 expression correlated with advanced tumor stage and shorter overall survival. LncUCA1 positively correlated with PD-L1 expression and activated the JAK2/STAT3 pathway in CAFs. Co-culture experiments showed high LncUCA1 CAFs inhibited CD8 T cell proliferation and enhanced immunosuppression. LncUCA1 overexpression enhanced matrix contraction but significantly promoted proliferation, migration, and invasion of OSCC cells.

CONCLUSIONS

LncUCA1 upregulation in CAFs drives PD-L1 expression, inhibits CD8 T cell proliferation, and promotes immunosuppression. High LncUCA1 CAFs also enhance OSCC proliferation, migration, and invasion.