LncRNA OSTM1-AS1 acts as an oncogenic factor in Wilms' tumor by regulating the miR-514a-3p/MELK axis

Anticancer Drugs. 2022 Sep 1;33(8):720-730. doi: 10.1097/CAD.0000000000001320. Epub 2022 Aug 10.

Abstract

Wilms' tumor (WT) is the most typical basic renal tumor in children and is associated with a high recurrence rate and improper diagnosis. Long noncoding RNAs (lncRNAs) play important roles in WT development. However, the impact of the OSTM1 antisense RNA 1 (OSTM1-AS1) lncRNA on WT remains largely unexplored. Differential expression of OSTM1-AS1, miR-514a-3p and maternal embryonic leucine zipper kinase (MELK) in mice with WT cells was assessed via quantitative reverse transcription-PCR and western blotting. Changes in the proliferation, migration and apoptosis of WT cells after OSTM1-AS1, miR-514a-3p or MELK knockdown were assessed using the cell counting kit-8, Transwell and caspase-3 activity assays, respectively. Additionally, the tumorigenicity of WT cells after OSTM1-AS1 knockdown in vivo was analyzed using a xenograft tumor assay. The association among OSTM1-AS1, MELK and miR-514a-3p was confirmed using the RNA binding protein immunoprecipitation and luciferase reporter assays. OSTM1-AS1 and MELK were upregulated in WT cells, whereas miR-514a-3p was downregulated. OSTM1-AS1 was mostly observed in the cytoplasm, and its knockout suppressed WT cell migration and proliferation in vitro , triggered apoptosis and attenuated tumor development in vivo . MiR-514a-3p was sponged by OSTM1-AS1, and miR-514a-3p interference counteracted the tumoricidal effect of OSTM1-AS1 knockdown. MiR-514a-3p reduced WT progression by downregulating the expression of MELK, which is the target gene of miR-514a-3p. lncRNA OSTM1-AS1 acts as an oncogenic factor in WT by releasing MELK through sponging miR-514a-3p and could be a useful target for WT diagnosis and therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms* / genetics
  • Membrane Proteins / genetics
  • Mice
  • MicroRNAs* / genetics
  • Protein Serine-Threonine Kinases* / genetics
  • RNA, Long Noncoding* / genetics
  • Ubiquitin-Protein Ligases / genetics
  • Wilms Tumor* / genetics

Substances

  • MIRN514 microRNA, human
  • Membrane Proteins
  • MicroRNAs
  • OSTM1 protein, human
  • OSTM1 protein, mouse
  • RNA, Long Noncoding
  • Ubiquitin-Protein Ligases
  • MELK protein, human
  • Protein Serine-Threonine Kinases