Arun Kanagaraj, Arunkumar Ganesan, Bennet Duraisamy, Chandramohan Servarayan Murugesan, Murugan Avaniyapuram Kannan, Munirajan Arasambattu Kannan
Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai - 600 113, India.
Institute of Surgical Gastroenterology, Rajiv Gandhi Government General Hospital and Madras Medical College, Chennai - 600 001, India.
Oncotarget. 2018 Apr 6;9(26):18386-18399. doi: 10.18632/oncotarget.24841.
Gastric cancer remains fifth most common cancer often diagnosed at an advanced stage and is the second leading cause of cancer-related death worldwide. Long non-coding RNAs (lncRNAs) involved in various cellular pathways are essential for tumor occurrence and progression and they have high potential to promote or suppress the expression of many genes. In this study, we profiled 19 selected cancer-associated lncRNAs in thirty gastric adenocarcinomas and matching normal tissues by qRT-PCR. Our results showed that most of the lncRNAs were significantly upregulated (12/19). Further, we performed bioinformatic screening of miRNAs that share common miRNA response elements (MREs) with lncRNAs and their downstream mRNA targets. The prediction identified three microRNAs (miR-21, miR-145 and miR-148a) and five gastric cancer-specific target genes (EGFR, KLF4, DNMT1 and AGO4) which also showed strong correlation with lncRNAs in regression analysis. Finally, we constructed an integrated lncRNA-miRNA-mRNA interaction network of the candidate genes to understand the post-transcriptional gene regulation. The ceRNA network analysis revealed that the differentially regulated miR-21 and miR-148a were playing as central candidates coordinating sponging activity of the lncRNAs analyzed (H19, TUG1 and MALAT1) in this study and the overexpression of H19 and miR-21 could be a signature event of gastric tumorigenesis that could serve as prognostic indicators and therapeutic targets.
胃癌仍然是第五大最常见的癌症,通常在晚期被诊断出来,并且是全球癌症相关死亡的第二大主要原因。参与各种细胞途径的长链非编码RNA(lncRNA)对于肿瘤的发生和发展至关重要,它们具有促进或抑制许多基因表达的巨大潜力。在本研究中,我们通过qRT-PCR分析了30例胃腺癌及配对正常组织中19种选定的癌症相关lncRNA。我们的结果表明,大多数lncRNA显著上调(12/19)。此外,我们对与lncRNA及其下游mRNA靶标共享共同miRNA反应元件(MRE)的miRNA进行了生物信息学筛选。预测鉴定出三种 microRNA(miR-21、miR-145和miR-148a)和五个胃癌特异性靶基因(EGFR、KLF4、DNMT1和AGO4),在回归分析中它们也与lncRNA显示出强相关性。最后,我们构建了候选基因的lncRNA-miRNA-mRNA综合相互作用网络,以了解转录后基因调控。ceRNA网络分析显示,差异调节的miR-21和miR-148a是本研究中协调所分析lncRNA(H19、TUG1和MALAT1)海绵活性的核心候选者,H19和miR-21的过表达可能是胃肿瘤发生的标志性事件,可作为预后指标和治疗靶点。