LncRNA FIRRE is activated by MYC and promotes the development of diffuse large B-cell lymphoma via Wnt/beta-catenin signaling pathway

摘要

Diffuse large B-cell lymphoma (DLBCL) contributes to the cancer-related mortality. Increasing evidence have reported the crucial role of long non-coding RNAs (lncRNAs) in tumorigenesis. Microarray analysis was used to screen out the differentially expressed lncRNAs. qRT-PCR proved that lncRNA functional intergenic repeating RNA element (FIRRE) was up-regulated in DLBCL tissues and cells. Based on Kaplan-Meier analysis, high FIRRE level was associated with the poor overall survival. Subsequently, cell functional assays further revealed that FIRRE functioned as an oncogene by promoting cell proliferation and reducing cell apoptosis in DLBCL. The upstream mechanism of FIRRE was analyzed in accordance with the bioinformatics analysis and mechanism experiments. The results showed that MYC proto-oncogene (MYC) contributed to the transcriptional activation of FIRRE in DLBCL cells. Further mechanism investigation prompted us to determine the association between Wnt/beta-catenin signaling pathway and FIRRE. Subcellular fractionation assay and western blot assay demonstrated that FIRRE activated Wnt/beta-catenin signaling pathway by promoting nuclear translocation of beta-catenin. Taken together, FIRRE activated Wnt/beta-catenin signaling pathway to facilitate DLBCL cell growth via modulation of the nuclear translocation of beta-catenin. Our findings reveals the novel molecular mechanism of FIRRE in DLBCL. (C) 2019 Elsevier Inc. All rights reserved.