Accumulating evidence has indicated that deregulation of lncRNAs plays essential roles in colorectal cancer (CRC) carcinogenesis. The goal of this study was to analyze the expression of lncRNAs in colorectal cancer and their association with clinicopathological variables. Bioinformatics analysis of published CRC microarray data was performed to identify the important lncRNAs. The expression levels of candidate genes were assessed in the human colon cancer/normal cell lines, CRC, adenomatous colorectal polyps, and their marginal tissues by qRT-PCR. Moreover, the methylation status of the TRPM2-AS1 promoter was studied using qMSP assay. Furthermore, we investigated the molecular mechanisms of these lncRNAs in CRC progression using in silico analysis. Microarray analysis revealed that lncRNAs SNHG6, MIR4435-2HG, and TRPM2-AS1 were upregulated in CRC. These results were validated in colon cell lines. Moreover, qRT-PCR showed that the expression levels of SNHG6 and TRPM2-AS1 were upregulated in the colorectal tumor tissues compared with their paired tissues. Nonetheless, there was no significant increase in MIR4435-2HG expression in CRC samples. Furthermore, we observed a significant hypomethylation of TRPM2-AS1 promoter and its activation in CRC tissues. By in silico analysis, we found that the lncRNAs upregulation could promote proliferation and drug resistance of colorectal cancer cells via miRNAs sponging and modulation of their targets expression. In conclusion, based on our results upregulation of SNHG6 and TRPM2-AS1, and hypomethylation of TRPM2-AS1 promoter might be considered as potential diagnostic biomarkers for CRC initiation and development.

中文翻译：

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lncRNAs SNHG6、TRPM2-AS1、MIR4435-2HG 的异常表达和 TRPM2-AS1 启动子在结直肠癌中的低甲基化

越来越多的证据表明，lncRNA 的失调在结直肠癌 (CRC) 的致癌作用中起着重要作用。本研究的目的是分析 lncRNA 在结直肠癌中的表达及其与临床病理变量的关联。对已发表的 CRC 微阵列数据进行生物信息学分析，以确定重要的 lncRNA。通过 qRT-PCR 在人结肠癌/正常细胞系、CRC、腺瘤性结直肠息肉及其边缘组织中评估候选基因的表达水平。此外，TRPM2-AS1的甲基化状态使用qMSP测定研究启动子。此外，我们使用计算机分析研究了这些 lncRNA 在 CRC 进展中的分子机制。微阵列分析显示，lncRNA SNHG6、MIR4435-2HG 和 TRPM2-AS1 在 CRC 中上调。这些结果在结肠细胞系中得到验证。此外，qRT-PCR 显示，与其配对组织相比，结直肠肿瘤组织中SNHG6和TRPM2-AS1的表达水平上调。尽管如此，CRC 样本中MIR4435-2HG的表达没有显着增加。此外，我们观察到TRPM2-AS1的显着低甲基化启动子及其在 CRC 组织中的激活。通过计算机分析，我们发现lncRNAs上调可以通过miRNAs海绵化和调节其靶标表达来促进结直肠癌细胞的增殖和耐药性。总之，根据我们的结果，SNHG6和TRPM2-AS1的上调和 TRPM2 -AS1启动子的低甲基化可能被认为是 CRC 起始和发展的潜在诊断生物标志物。