Long non-coding RNA PVT1 as a novel biomarker for diagnosis and prognosis of non-small cell lung cancer
Long non-coding RNA PVT1 as a novel biomarker for diagnosis and prognosis of non-small cell lung cancer
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DOI：
10.1007/s13277-015-4261-x
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发表时间：
2016-03-01
期刊：
影响因子：
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通讯作者：
Jiang, Wei-Long
中科院分区：
文献类型：
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作者：
Cui, Di;Yu, Cai-Hua;Jiang, Wei-Long
越来越多的证据表明，长链非编码RNA PVT1在各种人类癌症中上调。然而，目前尚不清楚PVT1是否参与非小细胞肺癌（NSCLC）的发生和进展。本研究旨在探讨PVT1在非小细胞肺癌中的表达、生物学作用及临床意义。我们的研究结果表明，PVT1在NSCLC组织和细胞系中表达显著升高，其表达上调与晚期t期、肿瘤淋巴结转移（TNM）期和区域淋巴结转移有关。PVT1表达水平在非小细胞肺癌组织与对照组的区分中表现强劲。Kaplan-Meier曲线和Cox回归分析显示，PVT1高表达与NSCLC患者总生存期和无病生存期差相关。3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑（MTT）和集落形成实验结果表明，PVT1的敲低可显著抑制NSCLC细胞增殖，而PVT1的过表达可显著促进细胞增殖。此外，PVT1敲低可增加G0/G1期细胞数量，减少S期细胞数量，而PVT1过表达可促进细胞周期进展。此外，我们的研究结果还揭示了PVT1小干扰RNA （siRNA）转染的NSCLC细胞中P15和P21的信使RNA （mRNA）和蛋白表达显著上调，pcDNA3.1-PVT1转染的细胞中P15和P21的mRNA和蛋白表达显著下调。综上所述，我们的研究表明PVT1可能是一个很有前景的非小细胞肺癌诊断和预后的生物标志物，它可以通过下调p15和p21的表达来促进非小细胞肺癌细胞的增殖。
Accumulating evidence has indicated that long non-coding RNA PVT1 is upregulated in various human cancers. However, it remains unclear whether PVT1 is involved in the development and progression of non-small cell lung cancer (NSCLC). The present study was designed to investigate the expression, biological role, and clinical significance of PVT1 in NSCLC. Our results indicated that PVT1 expression was significantly increased in NSCLC tissues and cell lines, and its upregulation was associated with advanced T-stage and tumor-node-metastasis (TNM) stage and regional lymph node metastasis. PVT1 expression levels were robust in differentiating NSCLC tissues from controls. Kaplan-Meier curve and Cox regression analysis showed that high expression of PVT1 was associated with poor overall survival and disease-free survival in NSCLC patients. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation assays indicated that knockdown of PVT1 remarkably inhibited NSCLC cell proliferation, whereas overexpression of PVT1 significantly promoted cellular proliferation. In addition, PVT1 knockdown increased the number of cells in the G0/G1 phase and reduced the number of cells in the S phase, while overexpression of PVT1 could promote cell cycle progression. Furthermore, our findings also revealed that the messenger RNA (mRNA) and protein expression of P15 and P21 was significantly upregulated in NSCLC cells transfected with PVT1 small interfering RNA (siRNA) and downregulated in cells transfected with pcDNA3.1-PVT1. In conclusion, our study demonstrated that PVT1 might serve as a promising biomarker for diagnosis and prognosis of NSCLC, and it could promote the proliferation of NSCLC cells by downregulating p15 and p21 expression.