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

Abstract

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.