Peng Wei, Wu Guoqiu, Fan Hong, Wu Jianzhong, Feng Jifeng
Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing Medical University, No. 42 Baiziting Road, Nanjing, 210009, China.
Laboratory of Cancer Research, Southeast University Affiliated Zhongda Hospital, No. 87 Dingjiaqiao Road, Nanjing, 210012, China.
Tumour Biol. 2015 Sep;36(9):6751-8. doi: 10.1007/s13277-015-3376-4. Epub 2015 Apr 3.
Gastric cancer (GC) is the second common cause of cancer-related death worldwide. Long noncoding RNAs (lncRNAs) are emerging as novel regulators in the cancer paradigm. However, investigation of lncRNAs on GC is still in its infancy. In this study, we focused on lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) and investigated its expression pattern, clinical significance, biological function, and molecular mechanism in GC. SPRY4-IT1 expression was examined, and its correlation with clinicopathological characteristics and patient prognosis was analyzed. A series of assays were performed to understand the role of SPRY4-IT1 in GC. SPRY4-IT1 expression was elevated in GC tissues and cell lines, and SPRY4-IT1 levels were highly positively correlated with tumor size, invasion depth, distant metastasis, TNM stage, and reduced overall survival (OS) and disease-free survival (DFS). A multivariate analysis showed that SPRY4-IT1 expression is an independent prognostic factor of OS and DFS in patients with GC. Additionally, the results of in vitro assays showed that the suppression of SPRY4-IT1 expression in GC cell line MKN-45 significantly reduced cell proliferation, colony formation, and cell migration/invasion. Moreover, the tumorigenic effects of SPRY4-IT1 were partially mediated by the regulation of certain cyclins and matrix metalloproteinases (MMPs)-related genes. Our data suggest that SPRY4-IT1 plays a critical role in GC tumorigenesis and may represent a novel prognostic marker and potential therapeutic target in patients with GC.
胃癌(GC)是全球癌症相关死亡的第二大常见原因。长链非编码RNA(lncRNAs)正在成为癌症模式中的新型调节因子。然而,关于lncRNAs在胃癌方面的研究仍处于起步阶段。在本研究中,我们聚焦于lncRNA SPRY4内含子转录本1(SPRY4-IT1),并研究了其在胃癌中的表达模式、临床意义、生物学功能及分子机制。检测了SPRY4-IT1的表达,并分析其与临床病理特征及患者预后的相关性。进行了一系列实验以了解SPRY4-IT1在胃癌中的作用。SPRY4-IT1在胃癌组织和细胞系中表达升高,且SPRY4-IT1水平与肿瘤大小、浸润深度、远处转移、TNM分期呈高度正相关,并与总生存期(OS)和无病生存期(DFS)降低相关。多因素分析表明,SPRY4-IT1表达是胃癌患者OS和DFS的独立预后因素。此外,体外实验结果显示,抑制胃癌细胞系MKN-45中SPRY4-IT1的表达可显著降低细胞增殖、集落形成及细胞迁移/侵袭。而且,SPRY4-IT1的致瘤作用部分是通过调控某些细胞周期蛋白和基质金属蛋白酶(MMPs)相关基因介导的。我们的数据表明,SPRY4-IT1在胃癌发生中起关键作用,可能是胃癌患者一种新的预后标志物和潜在治疗靶点。