College of Biology Sciences, Islamic Azad University, North Tehran Branch, Tehran, Iran.
Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Exp Mol Pathol. 2020 Oct;116:104490. doi: 10.1016/j.yexmp.2020.104490. Epub 2020 Jul 11.
The nuclear factor-κB (NF-κB) has a pivotal role in the pathogenesis of several cancers including gastric cancer. We have recently reported dysregulation of a number of NF-κB-associated lncRNAs in a variety of human disorders including breast cancer and coronary artery disease. In the current study, we evaluated expression of five NF-κB-associated lncRNAs (CHAST, ADINR, DICER1-AS1, HNF1A-AS1 and NKILA) and two NF-κB-associated-mRNA coding genes (CEBPA and ATG5) in gastric cancer tissues and their paired non-cancerous tissues using real time PCR method. Expression of DICER-AS1 was significantly down-regulated in gastric cancer tissues compared with the corresponding non-cancerous tissues (Expression ratio = 0.23, P value = .01). Expressions of other genes were not significantly different between these two sets of samples. Relative expression of DICER1-AS1 in cancer tissues versus non-cancerous tissues tended to associated with histological grade (P = .05). Tumoral expression levels of NKILA, ADINR, CEBPA and HNF1A-AS1 were significantly higher in patients with positive family history of cancer compared with those without such history (P values = .03, 0.02, 0.02 1nd 0.03, respectively). Besides, expression levels of NKILA, ADINR, DICER1-AS1, CEBPA, CHAST, HNF1A-AS1 and ATG5 were lower in H. pylori-infected tissues (P values = .01, 0.02, 0.03, 0.01, 0.004, 0.004 and 0.04, respectively). The lowest tumoral expression of DICER1-AS1 was detected in stage II cancers, while the highest expression of this lncRNA was reported in a single stage I tumor tissue. Similar pattern of expression was detected for ATG5. Significant pairwise correlations were demonstrated between expression levels of NF-ƙB-associated genes in both gastric cancer tissues and non-cancerous tissues. Expression levels of DICER1-AS1 had sensitivity and specificity values of 63.3% and 63.3% in differentiating between tumoral and non-tumoral tissues (Estimate criterion>6.96, J = 0.27, P value = .01, AUC = 0.67). Although previous studies have reported involvement of NF-κB pathway in the pathogenesis of gastric cancer, among the reported lncRNAs associated with this pathway, we could only detect differential expression of DICER1-AS1 between tumoral and non-tumoral tissues. Thus, the mechanism underlying dysregulation of this pathway might be different among various cancers.
核因子-κB(NF-κB)在包括胃癌在内的多种癌症的发病机制中起着关键作用。我们最近报道了 NF-κB 相关的长链非编码 RNA(lncRNA)在多种人类疾病中的失调,包括乳腺癌和冠状动脉疾病。在本研究中,我们使用实时 PCR 方法评估了五种 NF-κB 相关 lncRNA(CHAST、ADINR、DICER1-AS1、HNF1A-AS1 和 NKILA)和两种 NF-κB 相关 mRNA 编码基因(CEBPA 和 ATG5)在胃癌组织及其配对的非癌组织中的表达。与相应的非癌组织相比,胃癌组织中 DICER-AS1 的表达明显下调(表达比=0.23,P 值=0.01)。这两组样本之间其他基因的表达无显著差异。DICER1-AS1 在癌症组织与非癌症组织中的相对表达与组织学分级呈正相关(P=0.05)。与无家族史的患者相比,有癌症家族史的患者的肿瘤 NKILA、ADINR、CEBPA 和 HNF1A-AS1 表达水平明显更高(P 值分别为 0.03、0.02、0.02 和 0.03)。此外,H. pylori 感染组织中 NKILA、ADINR、DICER1-AS1、CEBPA、CHAST、HNF1A-AS1 和 ATG5 的表达水平较低(P 值分别为 0.01、0.02、0.03、0.01、0.004、0.004 和 0.04)。DICER1-AS1 在 II 期癌症中的肿瘤表达最低,而在单个 I 期肿瘤组织中报告的该 lncRNA 表达最高。ATG5 也表现出类似的表达模式。在胃癌组织和非癌组织中,NF-κB 相关基因的表达水平之间显示出显著的两两相关性。DICER1-AS1 在区分肿瘤和非肿瘤组织中的敏感性和特异性分别为 63.3%和 63.3%(估计标准>6.96,J=0.27,P 值=0.01,AUC=0.67)。尽管先前的研究报道了 NF-κB 通路在胃癌发病机制中的作用,但在所报道的与该通路相关的长链非编码 RNA 中,我们只能检测到 DICER1-AS1 在肿瘤组织和非肿瘤组织之间的差异表达。因此,不同癌症中该通路失调的机制可能不同。