Department of Hematology, The Affiliated Hospital of Qingdao University, No.16, Jiangsu Road, Qingdao, Shandong, 266003, China.
Department of Hematology, The Affiliated Hospital of Qingdao University, No.16, Jiangsu Road, Qingdao, Shandong, 266003, China.
Biochem Biophys Res Commun. 2019 Mar 19;510(4):594-600. doi: 10.1016/j.bbrc.2019.01.105. Epub 2019 Feb 7.
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/β-catenin signaling pathway and FIRRE. Subcellular fractionation assay and western blot assay demonstrated that FIRRE activated Wnt/β-catenin signaling pathway by promoting nuclear translocation of β-catenin. Taken together, FIRRE activated Wnt/β-catenin signaling pathway to facilitate DLBCL cell growth via modulation of the nuclear translocation of β-catenin. Our findings reveals the novel molecular mechanism of FIRRE in DLBCL.
弥漫性大 B 细胞淋巴瘤（DLBCL）是导致癌症相关死亡的原因之一。越来越多的证据表明长非编码 RNA（lncRNA）在肿瘤发生中起着关键作用。采用微阵列分析筛选差异表达的 lncRNA。qRT-PCR 证实 lncRNA 功能性基因间重复 RNA 元件（FIRRE）在 DLBCL 组织和细胞中上调。基于 Kaplan-Meier 分析，高 FIRRE 水平与总体生存率降低相关。随后，细胞功能测定进一步表明，FIRRE 通过促进细胞增殖和减少细胞凋亡在 DLBCL 中发挥癌基因作用。根据生物信息学分析和机制实验分析了 FIRRE 的上游机制。结果表明，原癌基因 MYC（MYC）促进了 DLBCL 细胞中 FIRRE 的转录激活。进一步的机制研究促使我们确定 Wnt/β-catenin 信号通路与 FIRRE 之间的关联。亚细胞分级分析和 Western blot 分析表明，FIRRE 通过促进 β-catenin 的核转位激活 Wnt/β-catenin 信号通路。总之，FIRRE 通过调节 β-catenin 的核转位激活 Wnt/β-catenin 信号通路，促进 DLBCL 细胞生长。我们的研究结果揭示了 FIRRE 在 DLBCL 中的新分子机制。
