Abstract
Germinal center B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) is a common subtype of lymphoma in adults. Previously, we found that actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1) is among the most overexpressed lncRNAs in GCB-DLBCL. In this study, we explored its biological functions and molecular mechanisms in the progression of GCB-DLBCL. We discovered, via bioinformatics, that patients with a high expression of AFAP1-AS1 had significantly poor disease-free survival (DFS) and overall survival (OS). Subsequent assays demonstrated that AFAP1-AS1 knockdown inhibited cell proliferation and prompted arrest of the G0/G1 cell cycle and apoptosis in GCB-DLBCL cell lines. Proteomics analysis indicated that hundreds of proteins were deregulated after AFAP1-AS1 knockdown and KEGG pathway analysis revealed that the deregulated proteins belonged to multiple signaling pathways, such as "B-cell receptor signaling pathway". Moreover, in the comprehensive identification of proteins that bind to RNA (by ChIRP-MS), several proteins associated with RNA splicing were identified (e.g., SFPQ, NONO, SRSF2, SRSF6, and KHSRP) that could specifically bind to AFAP1-AS1, which was confirmed by parallel reaction monitoring assay (PRM). Conclusively, we demonstrated that AFAP1-AS1 is a possible prognostic marker of poor outcomes in GCB-DLBCL patients and could modulate gene expression through connecting to specific proteins to practice its oncogenic role in GCB-DLBCL.