MicroRNA-146a Inhibits Progression and Immune Evasion in Diffuse Large B-cell Lymphomas by Targeting Programmed Cell Death Ligand 1.

Abstract

Background: Earlier studies have highlighted the involvement of miRNA146a in tumor suppression indicating its potential to inhibit the progression of diffuse large B-cell lymphoma (DLBCL).

Objective: To identify programmed death-ligand 1 (PD-L1) as a candidate for further research, as it plays a key role in regulating immune checkpoints in cancer and is associated with the involvement of miRNA146a in immune regulation and the response to inflammation.

Methods: The expression of miR-146a and PD-L1 in DLBCL cells was detected using qPCR analysis. Subsequently, DLBCL cells (OCI-Ly-3 and OCI-Ly-7) were treated with either the miR-146a mimic or a blank plasmid. To assess immune evasion, DLBCL cells were cocultured with peripheral blood mononuclear cells, CD8+ T cells, or cytokine-induced killer cells. Furthermore, the target gene of miR-146a was predicted and validated.

Results: Compared to the normal B-cell line (NCB), the level of miR-146a was significantly lower in DLBCL cells. Additionally, overexpression of miR-146a significantly reduced DLBCL viability, invasion, and immune evasion while simultaneously promoting apoptosis. Our findings also confirmed that miR-146a targeted PD-L1. Finally, the upregulation of PD-L1 notably reversed the tumor suppressive effects of miR-146a on DLBCL.

Conclusion: Our study indicates that miR-146a inhibits the progression of DLBCL by enhancing antitumor immunity through the targeting of PD-L1. The therapeutic potential of this miRNA in lymphoma is highly desirable.