LncRNA SNHG16 Drives PD-L1-Mediated Immune Escape in Colorectal Cancer through Regulating miR-324-3p/ELK4 Signaling.

Abstract

Colorectal cancer (CRC) is a common malignancy that claims the life of many patients. Nucleolar RNA host gene 16 (SNHG16) has been identified as an oncogene in CRC development. However, the role and mechanism of SNHG16 in CRC remain unclear. A total of 27 cases of CRC tumor tissues and adjacent tissues were collected to investigate the expression and correlation among SNHG16, miR-324-3p, ELK4 and PD-L1 using qRT-PCR, western blot and Pearson analysis. Cell proliferation, migration and invasion abilities were determined using CCK-8 and transwell assays. The cytotoxicity of CD8 + T cells and the apoptosis of CD8⁺ T cells was evaluated by LDH assay and flow cytometry, respectively. Dual luciferase assay, RIP and ChIP methods were performed to verify molecular interactions. Our results showed that SNHG16, ELK4 and PD-L1 expression were abnormally elevated and miR-324-3p expression was decreased in tumor tissues from CRC patients and CRC cells. SNHG16 silencing resulted in suppression of cell growth, metastasis, and immune escape of CRC cells, which was reversed by miR-324-3p inhibitor and ELK4 overexpression. Mechanistically, SNHG16 acted as a competitive endogenous RNA to enhance ELK4 expression by sponging miR-324-3p, thereby provoking the transcription of PD-L1. Our results demonstrated that SNHG16 silencing led to the suppression of cell growth, metastasis, and immune escape of CRC cells through mediating miR-324-3p/ELK4/PD-L1 axis, offering promising targets for CRC treatment.