Long noncoding RNA OIP5-AS1 accelerates CDK14 expression to promote osteosarcoma tumorigenesis via targeting miR-223

Biomed Pharmacother. 2018 Oct:106:1441-1447. doi: 10.1016/j.biopha.2018.07.109. Epub 2018 Jul 24.

Abstract

The critical roles for long non-coding RNAs (lncRNAs) have been demonstrated for series of cancers, including osteosarcoma. Nevertheless, the accurate mechanism of lncRNAs in osteosarcoma is elusive. In this assay, mechanical researches are performed to investigate the effect and mechanism of lncRNA OIP5-AS1 in osteosarcoma tumorigenesis. Results revealed that OIP5-AS1 level was elevated in osteosarcoma tissue and cells. Clinically, OIP5-AS1 high-expression was closely correlated with osteosarcoma patients' poor prognosis. Mechanistically, silenced OIP5-AS1 expression significantly repressed the proliferative ability and accelerated the apoptosis, meanwhile triggered G0/G1 phase cycle arrest in vitro and mice neoplasm growth in vivo. Subsequently, miR-223 was predicted to target the 3'-UTR of OIP5-AS1 and constituted RNA induced silencing complex, which was confirmed by RNA immunoprecipitation and luciferase reporter assay. Besides, miR-223 targeted the CDK14 mRNA 3'-UTR. In conclusion, our study found the critical regulation of OIP5-AS1/miR-223/CDK14 axis on osteosarcoma tumorigenesis, indicating the tumor promoting role of OIP5-AS1 for osteosarcoma.

Keywords: CDK14; Keyword; OIP5-AS1; Osteosarcoma; miR-223.

MeSH terms

  • 3' Untranslated Regions
  • Adolescent
  • Animals
  • Apoptosis
  • Binding Sites
  • Bone Neoplasms / enzymology*
  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Proliferation
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism*
  • Female
  • Gene Expression Regulation, Enzymologic
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Osteosarcoma / enzymology*
  • Osteosarcoma / genetics
  • Osteosarcoma / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Time Factors
  • Young Adult

Substances

  • 3' Untranslated Regions
  • MIRN223 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long noncoding RNA OIP5, human
  • CDK14 protein, human
  • Cyclin-Dependent Kinases