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Long-Chain Noncoding RNA ADAMTS9-AS2 Regulates Proliferation, Migration, and Apoptosis in Bladder Cancer Cells

Qing Guo1, Pinghua Ni1, Yi Dai1

  • 1Department of Urinary Surgery, The Fifth People's Hospital of Kunshan, Suzhou City, China.

Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
|February 23, 2021
PubMed

Insights

The long-chain noncoding RNA ADAMTS9-AS2 acts as a tumor suppressor in bladder cancer (BC). It inhibits BC cell proliferation and induces apoptosis by targeting miR-182-5p, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Long-chain noncoding RNAs (lncRNAs) play crucial roles in cancer development.
  • ADAMTS9-AS2 is recognized as a tumor suppressor in various cancers, but its role in bladder cancer (BC) requires further investigation.
  • Understanding the molecular mechanisms of lncRNAs in BC is vital for developing novel therapeutic strategies.

Purpose of the Study:

  • To elucidate the function and mechanism of ADAMTS9-AS2 in bladder cancer.
  • To investigate the relationship between ADAMTS9-AS2 and its target microRNA in BC progression.
  • To evaluate ADAMTS9-AS2 as a potential therapeutic target for bladder cancer.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) to assess ADAMTS9-AS2 expression levels in BC tissues and cell lines.
  • Cell proliferation, migration, and apoptosis assays (e.g., EdU, Transwell, TUNEL) following ADAMTS9-AS2 overexpression or inhibition.
  • MicroRNA (miRNA) target prediction and validation using luciferase reporter assays and Western blotting.
  • Rescue experiments to confirm the role of the ADAMTS9-AS2/miR-182-5p axis in BC cell behavior.

Main Results:

  • ADAMTS9-AS2 expression was significantly downregulated in bladder cancer samples and cell lines compared to normal controls.
  • Overexpression of ADAMTS9-AS2 suppressed bladder cancer cell proliferation and migration while inducing apoptosis in T24 cells.
  • Transfection with an ADAMTS9-AS2 inhibitor promoted proliferation and migration in 5637 cells.
  • ADAMTS9-AS2 directly targets and inhibits miR-182-5p, with inverse correlation observed between their expression levels.
  • Upregulation of miR-182-5p counteracted the tumor-suppressive effects of ADAMTS9-AS2 in T24 cells.

Conclusions:

  • ADAMTS9-AS2 functions as a tumor suppressor in bladder cancer by inhibiting cell proliferation and promoting apoptosis.
  • The tumor-suppressive activity of ADAMTS9-AS2 is mediated through its targeting of miR-182-5p.
  • ADAMTS9-AS2 represents a promising therapeutic target for bladder cancer treatment.
Keywords:
ADAMTS9-AS2apoptosisbladder cancermiR-182-5pproliferation

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