LncRNA DICER1-AS1 Promotes the Proliferation, Invasion and Autophagy of Osteosarcoma Cells via miR-30b/ATG5

Biomed Pharmacother. 2018 Aug;104:110-118. doi: 10.1016/j.biopha.2018.04.193. Epub 2018 May 15.

Abstract

Osteosarcoma is a prevalent primary malignant tumor and long non-coding RNAs (lncRNAs) have been validated to modulate the osteosarcoma tumorigenesis. In present study, our research team investigates the role of a novel identified lncRNA DICER1-AS1 on the tumor progression and autophagy. Results showed that lncRNA DICER1-AS1 was up-regulated in osteosarcoma cells using microarray analysis and RT-PCR. Cellular functional experiments revealed that DICER1-AS1 knockdown suppressed the proliferation, migration, invasion and autophagy of osteosarcoma cells in vitro. Besides, DICER1-AS1 knockdown inhibited the protein expression levels of ATG5, LC3-II and Beclin 1, suggesting the inhibition on the autophagy of osteosarcoma cells. Moreover, miR-30b was verified to target 3'-UTR of DICER1-AS1 and ATG5 using bioinformatics tools and luciferase reporter assay or RNA-immunoprecipitation (RIP). Western blot showed that ATG5 protein expression was decreased in DICER1-AS1 knockdown and miR-30b mimics transfected cells, while increased in miR-30b inhibitor transfected cells, presenting a negative correlation with miR-30b and a positive correlation with DICER1-AS1. Finally, xenograft assay in vivo indicated that DICER1-AS1 knockdown inhibited the osteosarcoma tumor growth and protein expression level of ATG5. In summary, all the results conclude that DICER1-AS1 regulates the proliferation, invasion and autophagy of osteosarcoma via miR-30b/ATG5 axis, providing a novel insight for osteosarcoma tumorigenesis.

Keywords: ATG5; Autophagy; DICER1-AS1; Osteosarcoma; miR-30b.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Autophagy / genetics*
  • Autophagy-Related Protein 5 / genetics*
  • Beclin-1 / genetics
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics*
  • DEAD-box RNA Helicases / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • MicroRNAs / genetics*
  • Microtubule-Associated Proteins / genetics
  • Osteosarcoma / genetics*
  • Osteosarcoma / pathology
  • RNA, Long Noncoding / genetics*
  • Ribonuclease III / genetics*
  • Up-Regulation / genetics

Substances

  • 3' Untranslated Regions
  • ATG5 protein, human
  • Autophagy-Related Protein 5
  • Beclin-1
  • MIRN30 microRNA, human
  • MicroRNAs
  • Microtubule-Associated Proteins
  • RNA, Long Noncoding
  • DICER1 protein, human
  • Ribonuclease III
  • DEAD-box RNA Helicases