HuR facilitates cancer stemness of lung cancer cells via regulating miR-873/CDK3 and miR-125a-3p/CDK3 axis

Biotechnol Lett. 2018 Apr;40(4):623-631. doi: 10.1007/s10529-018-2512-9. Epub 2018 Jan 17.

Abstract

Objectives: To study the roles and mechanisms of HuR in cancer stem cell maintenance of lung cancer.

Results: HuR expression was increased in tumor spheres of lung cancer cells. Knockdown of HuR suppressed spheroid formation and size, inhibited the expression of stemness-related marker, Oct4, Nanog and ALDH in lung cancer cells. Importantly, HuR and CDK3 expressions were increased in lung cancer tissues compared with normal adjacent tissues, and positively correlated. Mechanistically, HuR directly bound to CDK3, and increased CDK3 mRNA stability and expression. Additionally, miR-873 or miR-125a-3p attenuated the promotion of HuR on CDK3 expression and lung cancer stemness. Furthermore, HuR facilitated lung cancer stemness dependent on CDK3 expression. miR-873 or miR-125a-3p level was negatively correlated with HuR and CDK3 expression levels in lung cancer tissues.

Conclusions: HuR facilitates lung cancer stemness via regulating miR-873/CDK3 and miR-125a-3p/CDK3 axis.

Keywords: CDK3; HuR; Lung cancer; Stemness; miR-125a-3p; miR-873.

MeSH terms

  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cyclin-Dependent Kinase 3 / genetics*
  • ELAV-Like Protein 1 / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • Neoplastic Stem Cells / pathology
  • Signal Transduction / genetics

Substances

  • ELAV-Like Protein 1
  • ELAVL1 protein, human
  • MIRN125 microRNA, human
  • MIRN873 microRNA, human
  • MicroRNAs
  • CDK3 protein, human
  • Cyclin-Dependent Kinase 3