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Long non-coding RNA AFAP1-AS1 promotes cell growth and inhibits apoptosis by binding to specific proteins in germinal center B-cell-like diffuse large B-cell lymphoma

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.

SUBMITTER: Gao H

PROVIDER: S-EPMC7791486 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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LncRNA OR2A1-AS1 index predicts survival in germinal center-like diffuse large B-cell lymphoma.

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Long non-coding RNA AFAP1-AS1/miR-320a/RBPJ axis regulates laryngeal carcinoma cell stemness and chemoresistance.

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| S-EPMC8095348 | biostudies-literature

BCL2 predicts survival in germinal center B-cell-like diffuse large B-cell lymphoma treated with CHOP-like therapy and rituximab.

Project description:PurposeWe have previously shown the prognostic significance of BCL2 expression in the activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) patients treated with cyclophosphamide-Adriamycin-vincristine-prednisone (CHOP) or CHOP-like therapy. However, after the inclusion of rituximab (R) in the CHOP regimen, several conflicting observations about the prognostic value of BCL2 expression have been reported.Experimental designWe evaluated the R-CHOP cohort of 221 DLBCL cases with gene expression profiling data. BCL2 protein (n = 169), mRNA (n = 221) expression, and t(14;18) (n = 144) were correlated with clinical outcome. The CHOP cohort (n = 181) was used for comparative analysis.ResultsBCL2 protein expression has significant impact on overall survival (OS) and event-free survival (EFS) in DLBCL (OS, P = 0.009; EFS, P = 0.001) and GCB-DLBCL (OS, P = 0.03; EFS, P = 0.002) but not in ABC-DLBCL in the R-CHOP cohort. The survival differences for EFS in GCB-DLBCL were still observed in multivariate analysis. At the mRNA level, this correlation was observed in EFS in DLBCL (P = 0.006), but only a trend was observed in GCB-DLBCL (P = 0.09). The t(14;18) was detected in 34% of GCB-DLBCL but was not associated with significant differences in survival. Gene enrichment analysis identified significant enrichment of the DLBCL "stromal-1" signatures and hypoxia-inducible factor 1 (HIF1-α) signature in BCL2(-)GCB-DLBCL, whereas T(FH) cell signatures were enriched in BCL2(+)GCB-DLBCL.ConclusionThe prognostic significance of BCL2 has changed after inclusion of rituximab in the treatment protocol and is observed in the GCB-DLBCL rather than the ABC-DLBCL. Although rituximab has benefited patients in both DLBCL subgroups, the BCL2(+)GCB-DLBCL seems to receive less benefit from this treatment and may require other novel therapeutic intervention.

| S-EPMC7394278 | biostudies-literature

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