Long noncoding RNA negative regulator of antiviral response contributes to pancreatic ductal adenocarcinoma progression via targeting miR-299-3p

World J Gastroenterol. 2022 Sep 21;28(35):5141-5153. doi: 10.3748/wjg.v28.i35.5141.

Abstract

Background: Pancreatic ductal cancer (PDAC) has high malignancy and poor prognosis. Long noncoding RNAs (lncRNAs) are associated with high levels of malignancy, including PDAC. However, the biological and clinical significance of negative regulator of antiviral response (NRAV) in PDAC is unclear.

Aim: To study the regulatory role of lncRNA NRAV in PDAC.

Methods: GEPIA analyzed lncRNA NRAV and miRNA (miR-299-3p) expression levels in PDAC tissues and measured them in PDAC cells by quantitative measurements in real time. The specific role of NRAV and miR-299-3p in cell proliferation and transfer potential was evaluated by cell formation analysis, Cell Counting Kit-8 and Transwell analysis. The relationship between NRAV and miR-299-3p was studied by predictive bioinformatics, RNA immunoassay, and fluorescence enzyme analysis. In vivo experiments included transplantation of simulated tumor cells under naked mice.

Results: The expression level of lncRNA NRAV was higher in both tumor tissues and cell lines of PDAC and was negatively associated with the clinical survival of PDAC patients. Functionally, overexpression of NRAV promoted cell proliferation and metastasis of PDAC cells, while knockdown of NRAV reversed these effects. Finally, NRAV was performed as a molecular sponge of miR-299-3p. Moreover, overexpression of miR-299-3p could reverse the promoting effects of NRAV on cell proliferation and metastasis of PDAC cells.

Conclusion: NRAV facilitates progression of PDAC as a molecular sponge of miR-299-3p and may be a potential molecular marker for diagnosis and treatment of PDAC.

Keywords: Invasion; Long noncoding RNA; Migration; Negative regulator of antiviral response; Pancreatic cancer; Proliferation; miR-299-3p.

MeSH terms

  • Animals
  • Antiviral Agents
  • Carcinoma, Pancreatic Ductal* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Pancreatic Neoplasms* / pathology
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • Antiviral Agents
  • MicroRNAs
  • RNA, Long Noncoding