miR-216a inhibits osteosarcoma cell proliferation, invasion and metastasis by targeting CDK14

Cell Death Dis. 2017 Oct 12;8(10):e3103. doi: 10.1038/cddis.2017.499.

Abstract

Osteosarcoma (OS) has emerged as the most common primary musculoskeletal malignant tumour affecting children and young adults. Cyclin-dependent kinases (CDKs) are closely associated with gene regulation in tumour biology. Accumulating evidence indicates that the aberrant function of CDK14 is involved in a broad spectrum of diseases and is associated with clinical outcomes. MicroRNAs (miRNAs) are crucial epigenetic regulators in the development of OS. However, the essential role of CDK14 and the molecular mechanisms by which miRNAs regulate CDK14 in the oncogenesis and progression of OS have not been fully elucidated. Here we found that CDK14 expression was closely associated with poor prognosis and overall survival of OS patients. Using dual-luciferase reporter assays, we also found that miR-216a inhibits CDK14 expression by binding to the 3'-untranslated region of CDK14. Overexpression of miR-216a significantly suppressed cell proliferation, migration and invasion in vivo and in vitro by inhibiting CDK14 production. Overexpression of CDK14 in the miR-216a-transfected OS cells effectively rescued the suppression of cell proliferation, migration and invasion caused by miR-216a. In addition, Kaplan-Meier analysis indicated that miR-216a expression predicted favourable clinical outcomes for OS patients. Moreover, miR-216a expression was downregulated in OS patients and was negatively associated with CDK14 expression. Overall, these data highlight the role of the miR-216a/CDK14 axis as a novel pleiotropic modulator and demonstrate the associated molecular mechanisms, thus suggesting the intriguing possibility that miR-216a activation and CDK14 inhibition may be novel and attractive therapeutic strategies for treating OS patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Binding Sites / genetics
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology*
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • Cyclin-Dependent Kinases / biosynthesis*
  • Cyclin-Dependent Kinases / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Kaplan-Meier Estimate
  • Mice, Inbred BALB C
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Metastasis / genetics
  • Neoplasm Transplantation
  • Osteosarcoma / genetics
  • Osteosarcoma / pathology*
  • Transplantation, Heterologous

Substances

  • 3' Untranslated Regions
  • MIRN216 microRNA, human
  • MicroRNAs
  • CDK14 protein, human
  • Cyclin-Dependent Kinases