Long noncoding RNA CASC9 promotes pancreatic cancer progression by acting as a ceRNA of miR-497-5p to upregulate expression of CCND1

Environ Toxicol. 2023 Jun;38(6):1251-1264. doi: 10.1002/tox.23761. Epub 2023 Mar 22.

Abstract

Background: Pancreatic cancer (PC) is an aggressive malignancy with poor prognosis. Accumulating studies have showed that long non-coding RNA (lncRNA) is a crucial regulator in various tumorigenesis and progression including PC. This research aims to explore the roles and molecular mechanism of lncRNA cancer susceptibility candidate 9 (CASC9) in PC.

Methods: The expression levels of lncRNA CASC9 and miR-497-5p were evaluated in PC tissues and paired adjacent healthy tissues by quantitative real-time PCR. PC cell lines were transfected with lentivirus targeting lncRNA CASC9, and cells proliferation, migration and invasion tests were conducted. Dual luciferase reporter assays were also carried out to explore the relationship between lncRNA CASC9, miR-497-5p and Cyclin D1 (CCND1).

Results: LncRNA CASC9 was significantly up-regulated in PC tissues, while miR-497-5p expression was down-regulated. Down-regulation of lncRNA CASC9 in PC cells can significantly suppress the cell aggressiveness both in vitro and in vivo; moreover, knock-down of miR-497-5p could neutralize this impact. Additionally, the luciferase activity assay has assured that CCND1 was a downstream target of miR-497-5p.

Conclusion: LncRNA CASC9 can promote the PC progression by modulating miR-497-5p/CCND1 axis, which is potential target for PC treatment.

Keywords: CCND1; lncRNA CASC9; miR-497-5p; pancreatic cancer; progression.

MeSH terms

  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Cyclin D1 / genetics
  • Cyclin D1 / metabolism
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Pancreatic Neoplasms* / genetics
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • Cyclin D1
  • CCND1 protein, human
  • MIRN497 microRNA, human