The novel lncRNA p4516 acts as a prognostic biomarker promoting gastric cancer cell proliferation and metastasis
The novel lncRNA p4516 acts as a prognostic biomarker promoting gastric cancer cell proliferation and metastasis
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新型lncRNA p4516作为促进胃癌细胞增殖和转移的预后生物标志物
DOI：
10.2147/cmar.s201793
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Ji, Jia-Fu
中科院分区：
文献类型：
--
作者：
Nie, Meng-Lin;Han, Jing;Ji, Jia-Fu
目的：新的证据表明，长链非编码RNA（lncRNA）参与肿瘤的发生和发展。通过对198例胃癌患者配对肿瘤组织和非肿瘤组织中lncRNA表达谱的初步研究，我们发现了一种新的lncRNA p4516，它与胃癌患者的预后密切相关。然而，p4516在胃癌发生中的确切生物学功能和潜在的分子机制仍不清楚。材料与方法：应用RNA荧光原位杂交（RNA-FISH）、胞质和核RNA提取及qRT-PCR技术检测p4516的亚细胞定位。在两种GC细胞系和142个原发性GC组织中使用qRT-PCR评估p4516的表达水平。分析p4516表达与胃癌临床病理参数的相关性。采用功能获得和功能丧失实验研究p4516在体外和体内增殖、迁移和侵袭中的作用。Western blotting和免疫组化染色检测蛋白表达水平。结果如下：LncRNA p4516主要定位于GC细胞的细胞核中，并且与正常胃粘膜来源的细胞GES-1相比，p4516在GC细胞中倾向于具有更高的表达水平。此外，p4516的高表达水平与GC患者的临床结局较差相关，并作为独立的预后生物标志物。功能分析表明，p4516在体内外均参与调控胃癌细胞的增殖、侵袭和迁移。此外，p4516还参与了胃癌细胞的上皮间质转化（EMT）。结论：本研究首次证实了新型lncRNA p4516在胃癌发生中的致癌作用。p4516高表达可作为判断胃癌预后的指标。
Purpose: Emerging evidence has shown that long noncoding RNAs (lncRNAs) participate in oncogenesis and tumor progression. We previously found a novel lncRNA p4516 which was closely associated with prognosis by preliminary study of lncRNA expression profile from paired tumors and nontumor tissues in 198 gastric cancer (GC) patients. However, the exact biological functions and the underlying molecular mechanisms of p4516 in gastric tumorigenesis still remain unclear. Materials and methods: The RNA fluorescence in situ hybridization (RNA-FISH) analysis, cytoplasmic and nuclear RNA isolation and qRT-PCR were applied to determine the subcellular localization of p4516. Expression levels of p4516 were assessed using qRT-PCR in both GC cell lines and in 142 primary GC tissues. Correlations between p4516 expression and GC patients’ clinicopathological parameters were analyzed. Gain- and loss-of-function experiments were employed to investigate the role of p4516 in proliferation, migration and invasion both in vitro and in vivo. In addition, Western blotting and immunohistochemical staining were used to examine the protein expression levels. Results: LncRNA p4516 was mainly localized in the nucleus of GC cells and p4516 tended to have higher expression levels in GC cells compared to the normal gastric mucosa-derived cells GES-1. Furthermore, higher expression levels of p4516 correlated with worse clinical outcomes in GC patients and acted as an independent prognostic biomarker. Functional analysis revealed that p4516 participated in the regulation of GC cell proliferation, invasion and migration both in vivo and in vitro. Moreover, p4516 was involved in epithelial–mesenchymal transition (EMT) in GC cells. Conclusion: Our study demonstrated the oncogenic role of novel lncRNA p4516 in the gastric carcinogenesis for the first time. High expression of p4516 may act as prognostic marker in patient with gastric cancer.