Long Noncoding RNA PVT1 Acts as a "Sponge" to Inhibit microRNA-152 in Gastric Cancer Cells

Long Noncoding RNA PVT1 Acts as a "Sponge" to Inhibit microRNA-152 in Gastric Cancer Cells
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DOI:
10.1007/s10620-017-4508-z
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发表时间:
2017-11-01
影响因子:
3.1
通讯作者:
Yang, Wen-qi
Yang, Wen-qi
中科院分区:
医学3区
文献类型:
--
作者:
Li, Ting;Meng, Xiang-ling;Yang, Wen-qi

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背景:PVT1在胃癌患者中表达上调,可能成为预测胃癌的一个新的生物标志物。然而,PVT1在胃癌中发挥作用的确切机制尚不清楚。目的研究PVT1对胃癌细胞miR-152表达的影响。方法采用实时定量聚合酶链式反应技术检测胃癌组织中PVT1和miR-152的表达水平。转染PVT1或siPVT1的GC细胞可检测到miR-152的表达。用荧光素酶活性检测miR-152对CD151或FGF2表达的调节,PVT1对miR-152表达的调节。结果PVT1基因在胃癌组织中表达上调,miR-152基因表达下调。MIR-152与胃癌组织中PVT1的表达呈负相关。在计算机分析的基础上,我们发现PVT1与miR-152有三个结合序列。PVT1可能通过调节miR-152而抑制miR-152的表达,上调CD151和FGF2的表达。结论PVT1可能是抑制胃癌细胞miR-152表达的“海绵”。PVT1是提高胃癌诊断和治疗水平的一个有前景的分子靶点。
Background PVT1 was up-regulated in patients with gastric cancer (GC) and might be as a novel biomarker for predicting GC. However, the exact mechanism of PVT1 exerting functions in GC was still poorly understood. Emerging evidence suggests that long noncoding RNAs may act as endogenous microRNA (miRNA) sponges to bind to miRNAs and regulate their function.Aim This study aimed to determine the function of PVT1 on miR-152 expression in GC cells.Methods The levels of PVT1 and miR-152 were determined in GC tissues by quantitative real-time PCR. The expression of miR-152 was detected in GC cells transfected with PVT1 plasmid or siPVT1. Luciferase assay was performed to verify the regulation of miR-152 to CD151 or FGF2 expression and PVT1 to miR-152 expression. The effects of PVT1 on the expression of CD151 and FGF2 were evaluated by Western blot.Results PVT1 was up-regulated in GC tissues than that in the matched normal tissues, and mRNA level of miR-152 was decreased. MiR-152 was negatively associated with PVT1 expression in GC tissues. Based on the in silico analysis, we found that PVT1 have three binding sequences for miR-152. Moreover, PVT1 might inhibit the expression of miR-152 and increased the expression of CD151 and FGF2 through regulating miR-152. PVT1 was positively associated with CD151 and FGF2 expression in GC tissues.Conclusions PVT1 might act as a "sponge" to inhibit miR-152 in gastric cancer cells. PVT1 is a promising molecular target to improve the diagnosis and therapy of GC.