CircRNA VIM silence synergizes with sevoflurane to inhibit immune escape and multiple oncogenic activities of esophageal cancer by simultaneously regulating miR-124/PD-L1 axis.

BACKGROUND

Circular RNA of vimentin (circ-VIM) is a predictor for poor prognosis of acute myeloid leukemia, but we had little information on its function in esophageal cancer (EC). Here we examined the effects of circ-VIM together with sevoflurane on immune escape and multiple oncogenic activities of EC.

METHODS

Bioinformatic tools, luciferase assay, and RNA immunoprecipitation were used to examine regulations between circ-VIM, miR-124-3p (miR-124), and PD-L1. CCK-8, wound healing, and Transwell assays were used to measure cell proliferation, migration, and invasion, respectively. The impacts of EC cells on cytotoxicity, proliferation, and apoptosis of CD8 T cells were examined using LDH assay, CFSE staining, and Annexin V/PI staining, respectively. The in vivo tumorigenesis and lung metastases were assessed using xenograft model and tail vein injection of EC cells.

RESULTS

Significant upregulation of circ-VIM and PD-L1 and downregulation of miR-124 were detected in EC tissues or cells. Circ-VIM sponged miR-124 and released its suppression on the downstream target PD-L1. Sevoflurane, independent of circ-VIM, also upregulated miR-124 to lower PD-L1 expression. By modulating miR-124/PD-L1 axis, silencing circ-VIM and applying sevoflurane both inhibited immune escape and multiple oncogenic activities of EC in vitro, and suppressed xenograft growth and lung metastases in vivo. The inactivation of Ras/ERK signaling pathway was involved in suppression of malignant phenotypes by silencing circ-VIM and sevoflurane treatment.

CONCLUSIONS

Silencing circ-VIM and applying sevoflurane, by separately regulating miR-124/PD-L1 axis, presented synergistic effects in inhibiting immune escape and multiple malignant phenotypes of EC cells.