METHODS: Our research focused on examining the function of lncRNAs in the development of colon cancer. To this end, we selected and analyzed a dataset (GSE104836) from the GEO database, which contained information about the expression of mRNAs and lncRNAs in both colon cancer tissues and normal adjacent paired tumor tissues. The DESeq2 R package in Bioconductor was used to identify differentially expressed lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) that showed differences in expression levels. Next, by literature review of previous studies, we chose two lncRNAs (FENDRR and LINC00092) for additional studies. To validate our findings, a series of tests were performed on a total of 31 tumor tissues and normal paired adjacent tumor tissues. The lncRNA expression levels were assessed in tumor tissues as well as in surrounding normal tumor tissues.
RESULTS: The data confirmed that just two particular lncRNAs, FENDRR and LINC00092, had considerably decreased expression levels throughout all stages of cancer. In addition, the survival assay was conducted using the GEPIA2 software, revealing that a reduced expression of FENDRR is correlated with a reduced overall survival. Furthermore, our investigation using receiver operating characteristic (ROC) methodology revealed that these two lncRNAs had significant discriminatory ability between colon cancer and normal tissues. To determine the cause of the decrease in the activity of these two long non-coding RNAs (lncRNAs), we used methylation-specific PCR (MSP) to examine the methylation pattern of their promoter regions. Our investigation revealed hypermethylation in the promoter regions of FENDRR and LINC00092 within tumor tissues compared to normal adjacent tumor tissues.
CONCLUSIONS: Taken together, our findings revealed the lncRNAs signatures as potential therapeutic targets and molecular diagnostic biomarkers in colon cancer. Furthermore, the evidence provided substantiates the important role of promoter methylation in regulating the expression levels for both of these lncRNAs.
方法:我们的研究集中于检查lncRNAs在结肠癌发展中的功能。为此,我们从GEO数据库中选择并分析了一个数据集(GSE104836),其中包含有关结肠癌组织和正常相邻配对肿瘤组织中mRNA和lncRNA表达的信息。Bioconductor中的DESeq2R包用于鉴定差异表达的lncRNA(DElncRNA)和显示表达水平差异的mRNA(DEmRNA)。接下来,通过对以往研究的文献回顾,我们选择了两个lncRNAs(FENDRR和LINC00092)用于其他研究。为了验证我们的发现,对总共31个肿瘤组织和正常配对的邻近肿瘤组织进行了一系列测试。在肿瘤组织以及周围正常肿瘤组织中评估lncRNA表达水平。
结果:数据证实只有两个特定的lncRNAs,FENDRR和LINC00092在癌症的所有阶段都具有显著降低的表达水平。此外,使用GEPIA2软件进行生存测定,FENDRR表达降低与总生存期降低相关。此外,我们使用受试者工作特征(ROC)方法进行的调查显示,这两种lncRNAs在结肠癌和正常组织之间具有显著的辨别能力.为了确定这两种长非编码RNA(lncRNAs)活性降低的原因,我们使用甲基化特异性PCR(MSP)检测其启动子区域的甲基化模式.我们的调查显示,与正常邻近肿瘤组织相比,肿瘤组织内FENDRR和LINC00092启动子区域的甲基化过度。
结论:综合来看,我们的研究结果揭示了lncRNAs作为结肠癌潜在的治疗靶点和分子诊断生物标志物.此外,提供的证据证实了启动子甲基化在调节这两种lncRNAs表达水平中的重要作用.