Zhang Er-Bao, Han Liang, Yin Dan-Dan, Kong Rong, De Wei, Chen Jinfei
Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, Jiangsu, China.
Med Oncol. 2014 May;31(5):914. doi: 10.1007/s12032-014-0914-7. Epub 2014 Mar 27.
Gastric cancer (GC) is one of the most frequent cancers worldwide. Recent studies have shown that long noncoding RNAs (lncRNAs) play critical roles in multiple biological processes, including oncogenesis. The present study aimed to evaluate the potential role of lncRNA H19 in GC. qRT-PCR was performed to investigate the expression of H19 in tumor tissues and corresponding non-tumor lung tissues from 80 patients with GC and in GC cell lines. The Kaplan-Meier method and Cox proportional hazards analysis were used to evaluate the association between H19 expression and overall survival time (OS). The biological significance of H19 was evaluated using siRNAs in vitro. We also constructed a c-Myc plasmid to investigate the cause of the altered expression of H19 in the progression of GC. The results show that lncRNA H19 is overexpressed in tumor tissues compared with adjacent normal tissues. An advanced tumor-node-metastasis stage was positively correlated with increased H19 expression (P < 0.001), and a high H19 expression was associated with poor OS and can be regarded as an independent predictor of the OS of GC patients (P = 0.042). MTT and colony formation assays confirmed that H19 expression affects GC cell proliferation in vitro. Furthermore, exogenous c-Myc significantly induces H19 expression, and the expression of H19 was positively correlated with the c-Myc levels in the 80 samples used in our study (Pearson correlation coefficient = -0.687). In conclusion, our study demonstrates that the altered expression of lncRNA H19, which is induced by c-Myc, is involved in the development and progression of GC by regulating cell proliferation and shows that H19 may be a potential diagnostic and prognostic target in patients with GC.
胃癌（GC）是全球最常见的癌症之一。最近的研究表明，长链非编码RNA（lncRNA）在包括肿瘤发生在内的多个生物学过程中发挥着关键作用。本研究旨在评估lncRNA H19在胃癌中的潜在作用。采用qRT-PCR检测80例胃癌患者肿瘤组织及相应的非肿瘤肺组织以及胃癌细胞系中H19的表达。采用Kaplan-Meier法和Cox比例风险分析评估H19表达与总生存时间（OS）之间的关联。在体外使用小干扰RNA（siRNA）评估H19的生物学意义。我们还构建了c-Myc质粒，以研究胃癌进展过程中H19表达改变的原因。结果显示，与相邻正常组织相比，lncRNA H19在肿瘤组织中过表达。肿瘤-淋巴结-转移（TNM）分期进展与H19表达增加呈正相关（P<0.001），H19高表达与较差的总生存期相关，可被视为胃癌患者总生存期的独立预测指标（P = 0.042）。MTT和集落形成试验证实，H19表达影响体外胃癌细胞增殖。此外，外源性c-Myc显著诱导H19表达，在我们研究使用 的80个样本中，H19的表达与c-Myc水平呈正相关（Pearson相关系数 = -0.687）。总之，我们的研究表明，由c-Myc诱导的lncRNA H19表达改变通过调节细胞增殖参与胃癌的发生和发展，表明H19可能是胃癌患者潜在的诊断和预后靶点。
