LINC00324 accelerates the proliferation and migration of osteosarcoma through regulating WDR66

J Cell Physiol. 2020 Jan;235(1):339-348. doi: 10.1002/jcp.28973. Epub 2019 Jun 21.

Abstract

Osteosarcoma (OS) is a type of malignancy featured with high morbidity and easy metastasis. Although past years have witnessed the great improvement in the treatments of OS, there remains a long way to go. Therefore, further research on the underlying molecular mechanism of OS progression is in imminent need. Long noncoding RNAs (lncRNA) are recognized as a cluster of transcripts over 200 bases. Increasing studies have unveiled their significant regulatory roles in cancers, including in osteosarcoma. Long intergenic non-protein coding RNA 324 (LINC00324) is a newly identified lncRNA exerting oncogenic functions in several cancers, but its role in OS is yet to be uncovered. Therefore, the present study planned to explore the role of LINC00324 in osteosarcoma. We first validated the upregulation of LINC00324 in OS tissues and cell lines and established its correlation with OS tumor progression and metastasis. Importantly, the prognostic significance of LINC00324 was identified in patients with OS. Gain- and loss-of-function assays revealed that LINC00324 accelerated cell proliferation and migration in OS. Mechanistically, we revealed that LINC00324 stabilized WD repeat-containing protein 66 (WDR66) messenger RNA through interacting with Hu antigen R. Rescue assays verified that WDR66 was required for the regulation of LINC00324 in promoting proliferation and migration of OS cells. In conclusion, the present study proved that LINC00324 accelerated the proliferation and migration of osteosarcoma cells through regulating WDR66, providing a new prognostic target for osteosarcoma.

Keywords: LINC00324; WDR66; migration; osteosarcoma; proliferation.

MeSH terms

  • Bone Neoplasms / genetics
  • Bone Neoplasms / pathology*
  • Calcium-Binding Proteins / genetics*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Male
  • Middle Aged
  • Osteosarcoma / genetics
  • Osteosarcoma / pathology*
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • Up-Regulation / genetics

Substances

  • Calcium-Binding Proteins
  • RNA, Long Noncoding
  • WDR66 protein, human