circ_0001006 Promotes Immune Escape in Non-small Cell Lung Cancer by Regulating the miR-320a/PD-L1 Axis.

Abstract

Background: Circular RNAs are involved in the tumorigenesis of various tumors, including Non-small cell lung cancer (NSCLC).

Objective: To investigate the expression of circ_0001006 in patients with NSCLC and its role in tumorigenesis and immune escape.

Methods: A total of 115 patients with NSCLC were enrolled in the study. The expression of circ_0001006 and PD-L1 mRNA were detected using RT-qPCR. Cell proliferation activity, cell migration and invasion abilities were measured using the CCK-8 assay and Transwell chambers assay. Coculture of NSCLC cells with CD8 cytotoxic T cells was conducted to measure the levels of INF-γ, TNF-α, IL-2, and lactate dehydrogenase release in culture supernatants. Bioinformatic analysis was used to predict the target relevance among circ_0001006, miR-320a, and PD-L1.

Results: The circ_0001006 and PD-L1 mRNA levels were elevated in NSCLC tissues and cells. Patients with high levels of circ_0001006 had a shorter overall survival rate. Inhibiting circ_0001006 reduced the proliferation, migration, and invasion of NSCLC cells, while increasing PD-L1 partially counteracting the inhibitory effects of si-circ_0001006. The co-culture system of NSCLC and CD8+ T cell was found to reduce the viability of activated CD8+ T cell when circ_0001006 is present. Knocking down circ_0001006 in co-culture cells led to an increase in the expression of INF-γ, TNF-α, and IL-2. The ability of si-circ_0001006 to enhance the activation of CD8+ T cells was diminished when PD-L1 was overexpressed.

Conclusion: circ_0001006 may serve as a potential prognostic predictor and therapeutic target for NSCLC. Additionally, it offers insight into a novel regulatory mechanism of circ_0001006.