LncRNA SOX21-AS1 Promotes the Growth and Invasiveness of Osteosarcoma Cells Through miR-7-5p/IRS2 Regulatory Network

Arch Med Res. 2021 Apr;52(3):294-303. doi: 10.1016/j.arcmed.2020.11.007. Epub 2020 Dec 17.

Abstract

Background: Osteosarcoma (OS) is commonly known as a bone malignancy, causing a mass of lethality worldwide. Long coding RNAs (lncRNAs) have been widely reported by documents that they exert important functions in the development of cancers. However, the relative mechanism of lncRNA SOX21-AS1 needs to be fully discovered in OS, as it has never been studied in the past.

Aim of the study: To find out how SOX21-AS1 materializes its function in OS.

Methods: qRT-PCR detected RNA expression, and western blot tested the protein level. CCK8 and TUNEL assays were performed to assess cell viability and apoptosis. Next, Transwell analyses were applied to identify OS cell migration and invasion. Luciferase reporter, RIP and RNA pull-down experiments were employed for investigating the relationships among RNAs.

Results: SOX21-AS1 had high expression in OS, and its presence accelerated OS cell proliferation, migration and invasion. Interestingly, we evidenced that SOX21-AS1 sponged miR-7-5p, which then targeted IRS2 in OS cells. SOX21-AS1 competed with IRS2 in binding to miR-7-5p, which formulated the ceRNA signaling in OS. SOX21-AS1 could negatively regulate miR-7-5p expression. Rescue experiments certified that the enhancement of IRS2 would neutralize the inhibition of SOX21-AS1 depletion on OS cell proliferation and metastasis.

Conclusions: SOX21-AS1 enhances IRS2 level by absorbing miR-7-5p, so as to boost the progression of OS.

Keywords: IRS2; Osteosarcoma; SOX21-AS1; miR-7-5p.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Heterografts
  • Humans
  • Insulin Receptor Substrate Proteins / genetics
  • Insulin Receptor Substrate Proteins / metabolism*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Osteosarcoma / genetics*
  • Osteosarcoma / metabolism
  • Osteosarcoma / pathology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Transfection

Substances

  • IRS2 protein, human
  • Insulin Receptor Substrate Proteins
  • MIRN7 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long noncoding RNA SOX21-AS1, human