Chen F, Tian Y, Pang E-J, Wang Y, Li L
Division of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Cancer Gene Ther. 2015 Feb 27. doi: 10.1038/cgt.2015.6.
The purpose of this study is to investigate the role of the long noncoding RNA metastasis associated lung adenocarcinoma transcript 2 (MALAT2) in the prognosis of stage II/III gastric cancer (GC) patients. The expression of MALAT2 was evaluated in cancer tissues from 146 stage II/III GC patients undergoing radical resection and 60 paired normal samples using quantitative real-time reverse transcriptase PCR. Differences in the expression of MALAT2 between 23 GC and paired normal colonic mucosa samples were analysed with the Wilcoxon test. Relationships between the expression level of MALAT2, patient clinico-pathological parameters and disease-free survival and overall survival were analysed using the uni-variate Kaplan-Meier method and the multivariate COX regression model. The quantitative polymerase chain reaction results showed that MALAT2 was frequently over-expressed in cancer tissues and this over-expression was found to significantly correlate with lymph node metastasis and tumor stage. The ectopic expression of MALAT2 contributed to the migration of human GC SGC-7901 cells, whereas knockdown of MALAT2 inhibited the migration of the SGC-7901 cells in vitro. Further investigation into the underlying mechanisms responsible for the migratory effects revealed that MALAT2 induced the epithelial-mesenchymal transition (EMT) through an MEK/extracellular signal-regulated kinase-dependent mechanism as treatment with the MEK inhibitor, U0126, decreased migration and reversed the EMT in the MALAT2 over-expressed SGC-7901 cells. The expression of MALAT2 is upregulated in GC tissues, and a higher expression level of MALAT2 might serve as a negative prognostic marker in stage II/III GC patients which implies the potential application of MALAT2 in the therapeutic treatment of GC.Cancer Gene Therapy advance online publication, 27 February 2015; doi:10.1038/cgt.2015.6.
本研究旨在探讨长链非编码RNA转移相关肺腺癌转录本2（MALAT2）在II/III期胃癌（GC）患者预后中的作用。采用定量实时逆转录聚合酶链反应，评估146例接受根治性切除的II/III期GC患者癌组织及60例配对正常样本中MALAT2的表达。用Wilcoxon检验分析23例GC及其配对正常结肠黏膜样本中MALAT2表达的差异。采用单变量Kaplan-Meier法和多变量COX回归模型分析MALAT2表达水平、患者临床病理参数与无病生存期及总生存期之间的关系。定量聚合酶链反应结果显示，MALAT2在癌组织中常过度表达，且这种过度表达与淋巴结转移和肿瘤分期显著相关。MALAT2的异位表达促进人GC SGC-7901细胞的迁移，而敲低MALAT2则在体外抑制SGC-7901细胞的迁移。对迁移效应潜在机制的进一步研究表明，MALAT2通过MEK/细胞外信号调节激酶依赖性机制诱导上皮-间质转化（EMT），因为用MEK抑制剂U0126处理可减少迁移并逆转MALAT2过表达的SGC-7901细胞中的EMT。MALAT2在GC组织中表达上调，MALAT2较高的表达水平可能作为II/III期GC患者的不良预后标志物，这意味着MALAT2在GC治疗中的潜在应用。《癌症基因治疗》在线优先发表，2015年2月27日；doi:10.1038/cgt.2015.6
