SLC52A3 expression is activated by NF-κB p65/Rel-B and serves as a prognostic biomarker in esophageal cancer.
SLC52A3 expression is activated by NF-κB p65/Rel-B and serves as a prognostic biomarker in esophageal cancer.
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SLC52A3 表达由 NF-kappa B p65/Rel-B 激活，可作为食管癌的预后生物标志物
DOI：
10.1007/s00018-018-2757-4
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Xu LY
中科院分区：
文献类型：
--
作者：
Long L;Pang XX;Lei F;Zhang JS;Wang W;Liao LD;Xu XE;He JZ;Wu JY;Wu ZY;Wang LD;Lin DC;Li EM;Xu LY
人核黄素转运蛋白-3 （SLC52A3编码）在核黄素吸收中起着重要作用。有趣的是，SLC52A3在多种类型的人类癌症中的异常表达模式最近已被注意到。然而，其失调的分子机制尚不清楚。在本研究中，我们发现SLC52A3有两个转录变异体，它们的转录起始位点不同，编码的蛋白也不同：SLC52A3a和SLC52A3b。重要的是，SLC52A3的异常表达与食管鳞状细胞癌（ESCC）的逐步发展以及ESCC患者的生存率相关。在功能上，SLC52A3a而不是SLC52A3b强烈促进ESCC细胞的增殖和集落形成。此外，SLC52A3 5 '侧区含有NF-κB p65/ rel -b结合位点，这对于介导SLC52A3在ESCC细胞中的转录活性至关重要。染色质免疫沉淀和电泳迁移率转移实验显示p65/Rel-B结合到SLC52A3的5 '侧区。因此，NF-κB信号在TNFα刺激下上调SLC52A3的转录。综上所述，这些结果阐明了SLC52A3在ESCC中过表达的机制。更重要的是，我们的研究结果确定SLC52A3是这种致命癌症的预测和预后生物标志物。本文的在线版本（10.1007/s00018-018-2757-4）包含补充资料，仅供授权用户使用。
The human riboflavin transporter-3 (encoded by SLC52A3) plays a prominent role in riboflavin absorption. Interestingly, abnormal expression patterns of SLC52A3 in multiple types of human cancers have been recently noted. However, the molecular mechanisms underlying its dysregulation remain unclear. In this study, we find that SLC52A3 has two transcript variants that differ in the transcriptional start site, and encode different proteins: SLC52A3a and SLC52A3b. Importantly, aberrant expressions of SLC52A3 are associated with stepwise development of esophageal squamous cell carcinoma (ESCC) as well as the survival rates of ESCC patients. Functionally, SLC52A3a, but not SLC52A3b, strongly promotes the proliferation and colony formation of ESCC cells. Furthermore, SLC52A3 5′-flanking regions contain NF-κB p65/Rel-B-binding sites, which are crucial for mediating SLC52A3 transcriptional activity in ESCC cells. Chromatin immunoprecipitation and electrophoretic mobility shift assay reveal that p65/Rel-B bind to 5′-flanking regions of SLC52A3. Accordingly, NF-κB signaling upregulates SLC52A3 transcription upon TNFα stimulation. Taken together, these results elucidate the mechanisms underlying SLC52A3 overexpression in ESCC. More importantly, our findings identify SLC52A3 as both a predictive and prognostic biomarker for this deadly cancer. The online version of this article (10.1007/s00018-018-2757-4) contains supplementary material, which is available to authorized users.
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影响因子：
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