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

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.

Keywords: ADINR; ATG5; CEBPA; CHAST; DICER1-AS1; Gastric Cancer; HNF1A-AS1; NKILA; lncRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy-Related Protein 5 / genetics
  • CCAAT-Enhancer-Binding Proteins / genetics
  • Cell Line, Tumor
  • DEAD-box RNA Helicases / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Male
  • Middle Aged
  • NF-kappa B / genetics
  • Neoplasm Staging
  • RNA, Long Noncoding / genetics*
  • Ribonuclease III / genetics*
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology

Substances

  • ATG5 protein, human
  • Autophagy-Related Protein 5
  • CCAAT-Enhancer-Binding Proteins
  • CEBPA protein, human
  • CEBPA-DT long noncoding RNA, human
  • NF-kappa B
  • RNA, Long Noncoding
  • long non-coding RNA HNF1A-AS1, human
  • long noncoding RNA NKILA, human
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases