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DICER-AS1 lncRNA:胃癌发病机制中的一个潜在罪魁祸首。

DICER-AS1 lncRNA: A putative culprit in the pathogenesis of gastric cancer.

机构信息

College of Biology Sciences, Islamic Azad University, North Tehran Branch, Tehran, Iran.

Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

Exp Mol Pathol. 2020 Oct;116:104490. doi: 10.1016/j.yexmp.2020.104490. Epub 2020 Jul 11.

Abstract

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.

摘要

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。

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