LncRNA CYTOR knockdown inhibits tumor development via regulating miR-503-5p/PCSK9 in lung adenocarcinoma

Am J Med Sci. 2024 Oct;368(4):382-391. doi: 10.1016/j.amjms.2024.07.012. Epub 2024 Jul 6.

Abstract

Background: The intricate biological mechanism underlying lung adenocarcinoma (LUAD), characterized by a deficiency of distinctive biomarkers, remain elusive. The presence of Long non-coding RNAs (lncRNAs) have been established to play a role in carcinogenesis. Nevertheless, the regulatory effects and mechanisms of lncRNA CYTOR in LUAD have yet to be elucidated.

Methods: In this study, RT-qPCR and Western blot were adopted to examine gene mRNA and protein expression, respectively. Cell proliferation was evaluated by CCK-8 assays. Transwell was performed to assay cell migration and invasion. The function of CYTOR in vivo was investigated through a xenograft animal model.

Results: We observed an apparent upregulation of CYTOR in LUAD. Silencing CYTOR significantly reduced proliferation, migration, and invasion capabilities of LUAD cells. Mechanism analysis indicated that CYTOR targeted the miR-503-5p/PCSK9 axis. Additionally, inhibiting of miR-503-5p partially reversed the inhibitory effects of CYTOR silencing on the malignant progression of LUAD cells. Animal experiments revealed that CYTOR/miR-503-5p/PCSK9 curbed tumor formation of nude mice in vivo.

Conclusion: These findings demonstrated that lncRNA CYTOR acted as an oncogene in LUAD, regulating tumor malignant progression through the miR-503-5p/PCSK9 axis. This study unveiled a new regulation mechanism of LUAD progression, offering potential therapeutic targets for LUAD.

Keywords: LUAD; LncRNA CYTOR; Malignant progression; PCSK9; miR-503-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Adenocarcinoma of Lung* / metabolism
  • Adenocarcinoma of Lung* / pathology
  • Animals
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation* / genetics
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Mice
  • Mice, Nude*
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Proprotein Convertase 9* / genetics
  • Proprotein Convertase 9* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • Proprotein Convertase 9
  • MIRN503 microRNA, human
  • PCSK9 protein, human