Long non-coding RNA SOX21-AS1 modulates lung cancer progress upon microRNA miR-24-3p/PIM2 axis

Bioengineered. 2021 Dec;12(1):6724-6737. doi: 10.1080/21655979.2021.1955578.

Abstract

Lung cancer is a lethal cancer that threatens human health. Several studies have demonstrated the role of long non-coding RNAs (lncRNAs) in lung cancer. SOX21-AS1 is a newly discovered oncogenic lncRNA, but its molecular mechanism in lung cancer is not known. Here, the levels of SOX21-AS1, miR-24-3p, and PIM2 were examined in lung cancer and normal tissues. The relationships between miR-24-3p and SOX21-AS1 or PIM2 were predicted using bioinformatics tools and confirmed using a luciferase reporter assays. Colony formation, MTT, flow cytometry, and transwell assays were conducted to analyze cell proliferation, apoptosis, migration, and invasion abilities, respectively. Western blotting was used to measure PIM2 expression levels in cancer tissues and cells. SOX21-AS1 expression levels were high in lung cancer tissues and cells. In contrast, the amount of miR-24-3p bound to SOX21-AS1 was relatively low in cancerous tissues and cells. The knockdown of SOX21-AS1 decreased cell proliferation, activated apoptosis, and promoted cell migration and invasion. These effects were abolished by miR-24-3p inhibition. The oncogenic function of SOX21-AS1 mediated through targeting miR-24-3p was also demonstrated in animal models. PIM2 was targeted by miR-24-3p and showed increased levels in tumor tissues and cells. Furthermore, miR-24-3p overexpression inhibited the proliferation and promoted the apoptosis of lung cancer cells. In lung cancer cells, SOX21-AS1 negatively modulated the miR-24-3p/PIM2 axis to facilitate their proliferation, migration, and invasion. These findings offer a novel idea for future research on treating lung cancer at the molecular level.

Keywords: Lung cancer; PIM2; SOX21-AS1; miR-24-3p.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Disease Progression
  • Humans
  • Lung / pathology
  • Lung Neoplasms* / genetics
  • Lung Neoplasms* / metabolism
  • Lung Neoplasms* / pathology
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism

Substances

  • MIRN24 microRNA, human
  • MicroRNAs
  • PIM2 protein, human
  • Proto-Oncogene Proteins
  • RNA, Long Noncoding
  • long noncoding RNA SOX21-AS1, human
  • Protein Serine-Threonine Kinases