The Human RNA Surveillance Factor UPF1 Modulates Gastric Cancer Progression by Targeting Long Non-Coding RNA MALAT1
The Human RNA Surveillance Factor UPF1 Modulates Gastric Cancer Progression by Targeting Long Non-Coding RNA MALAT1
复制标题
人类 RNA 监视因子 UPF1 通过靶向长非编码 RNA MALAT1 来调节胃癌进展。
DOI：
10.1159/000479994
复制
发表时间：
2017-01-01
影响因子：
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通讯作者：
Fei, Sujuan
中科院分区：
文献类型：
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作者：
Li, Li;Geng, Yingying;Fei, Sujuan
背景/目的：长链非编码RNA转移相关肺腺癌转录本1（MALAT 1）在许多癌症中过表达。然而，MALAT 1在胃癌中是否受到调控以及相关机制尚不清楚。研究方法：采用免疫组化和qRT-PCR方法检测UPF 1和MALAT 1在胃癌及癌旁正常组织中的表达水平。采用MTT法、细胞周期、细胞凋亡和transwell法检测UPF 1对细胞周期进程、细胞增殖、凋亡、迁移和侵袭的影响。采用硫酸氢钠测序法检测胃肿瘤组织中UPF 1基因启动子区甲基化水平。最后，RNA免疫沉淀和荧光素酶报告分析表明，UPF 1直接结合MALAT 1。结果：UPF 1在胃癌组织中的表达明显下调，且与MALAT 1表达呈负相关。UPF 1低表达组患者的预后较高表达组差。UPF 1过表达抑制胃癌细胞增殖、细胞周期进程、细胞迁移和侵袭，促进细胞凋亡。此外，UPF 1介导的胃癌进展抑制被MALAT 1过表达逆转。胃肿瘤组织中UPF 1的显著下调是由于启动子的高甲基化。UPF 1的过表达增加了无义介导的mRNA衰减（NMD）效率，从而导致MALAT 1的下调。结论：我们的研究结果表明，UPF 1是MALAT 1的一个潜在的调节剂，UPF 1/MALAT 1通路可能是胃癌的一个治疗靶点。(C)2017作者（s）由S. Karger AG，巴塞尔
Background/Aims: The long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overexpressed in numerous cancers. However, whether MALAT1 is regulated and the related mechanisms in gastric cancer remain unclear. Methods: Immunohistochemistry and qRT-PCR analyses were used to detect the expression levels of UPF1 and MALAT1 in gastric cancer and adjacent normal tissues. MTT, cell cycle, apoptosis and transwell assays were performed to examine the effects of UPF1 on cell cycle progression, cell proliferation, apoptosis, migration and invasion. Additionally, sodium bisulfate sequencing was used to test the promoter hypermethylation on UPF1 in gastric tumor tissues. Finally, RNA immunoprecipitation and luciferase reporter analyses demonstrated that UPF1 directly bound with MALAT1. Results: The expression of UPF1 was significantly downregulated in gastric cancer and negatively correlated with MALAT1 expression. Patients with lower expression of UPF1 had poorer prognosis than those with higher expression. Overexpression of UPF1 inhibited cell proliferation, cell cycle progression, cell migration and invasion, and promoted cell apoptosis in gastric cancer cells. Moreover, the UPF1-mediated inhibition of gastric cancer progression was reversed by overexpression of MALAT1. A profound downregulation of UPF1 in gastric tumor tissues was due to promoter hypermethylation. Overexpression of UPF1 increased nonsense-mediated mRNA decay (NMD) efficiency and thus led to downregulation of MALAT1. Conclusion: Our results demonstrate that UPF1 is a potential modulator of MALAT1 and that UPF1/MALAT1 pathway could be a therapeutic target for gastric cancer. (C) 2017 The Author(s) Published by S. Karger AG, Basel