Long noncoding RNA NORAD regulates cancer cell proliferation and migration in human osteosarcoma by endogenously

Xuming Wang1, Jilong Zou1, Hongjun Chen1

  • 1Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, China.

IUBMB Life
|June 7, 2019
PubMed

Insights

The long noncoding RNA NORAD is overexpressed in osteosarcoma and promotes cancer cell proliferation and invasion. Inhibiting NORAD suppressed tumor growth, suggesting NORAD is a potential therapeutic target for osteosarcoma.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • Osteosarcoma is a primary bone malignancy with limited treatment options.
  • Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in cancer development.
  • NORAD (Noncoding RNA activated by DNA damage) is a lncRNA implicated in various cancers.

Purpose of the Study:

  • To investigate the expression and function of NORAD in human osteosarcoma.
  • To elucidate the molecular mechanism underlying NORAD's role in osteosarcoma progression.
  • To assess NORAD as a potential therapeutic target for osteosarcoma.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) for NORAD expression analysis in cell lines and patient tumors.
  • siRNA-mediated NORAD downregulation in osteosarcoma cells (Saos-2, 143B).
  • Functional assays including CCK-8 proliferation, Transwell invasion, and in vivo tumor explant studies.
  • Dual-luciferase reporter assay and qRT-PCR to confirm NORAD-hsa-miR-199a-3p interaction.

Main Results:

  • NORAD was significantly overexpressed in osteosarcoma cell lines and clinical specimens.
  • NORAD downregulation suppressed osteosarcoma cell proliferation, invasion, and in vivo tumor growth.
  • NORAD was confirmed to competitively bind hsa-miR-199a-3p.
  • Downregulation of hsa-miR-199a-3p reversed the tumor-suppressive effects of NORAD inhibition.

Conclusions:

  • NORAD plays a crucial oncogenic role in osteosarcoma by promoting cell proliferation and invasion.
  • The NORAD/hsa-miR-199a-3p axis is a key regulatory pathway in osteosarcoma.
  • NORAD represents a promising therapeutic target for osteosarcoma treatment.

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