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MIR503HG impeded ovarian cancer progression by interacting with SPI1 and preventing TMEFF1 transcription

Jun Tian1, Lei Yang2, Zhongtai Wang3

  • 1Department Gynecology, HuaiHe Hospital of HeNan University, Kaifeng, HeNan, China.

Aging
|June 30, 2022
PubMed

Insights

MIR503 host gene (MIR503HG) suppresses ovarian cancer progression by inhibiting SPI1-mediated TMEFF1 activation. Overexpression of MIR503HG reduces proliferation and invasion, while its silencing promotes these malignant behaviors.

Area of Science:

  • Molecular Biology
  • Oncology
  • Genetics

Background:

  • The MIR503 host gene (MIR503HG) is recognized as a tumor suppressor in various human cancers.
  • Its specific function and regulatory mechanisms in ovarian cancer remain incompletely understood.

Purpose of the Study:

  • To investigate the role of MIR503HG in ovarian cancer.
  • To elucidate the molecular mechanisms underlying MIR503HG's function in ovarian cancer.

Main Methods:

  • Quantitative real-time PCR to assess MIR503HG expression levels.
  • Cell proliferation, invasion, apoptosis, and EMT assays to evaluate MIR503HG function.
  • RNA immunoprecipitation, RNA pull-down, dual luciferase reporter, and Chromatin immunoprecipitation assays to determine molecular interactions.
  • Western blotting to analyze pathway activation.
  • In vivo tumorigenesis assays in nude mice.

Main Results:

  • MIR503HG expression was significantly lower in ovarian tumor tissues and cells compared to normal controls.
  • MIR503HG overexpression inhibited ovarian cancer cell proliferation, invasion, and epithelial-mesenchymal transition (EMT), while promoting apoptosis.
  • MIR503HG directly binds to transcription factor SPI1, inhibiting SPI1-mediated transcriptional activation of TMEFF1.
  • MIR503HG knockdown led to increased TMEFF1 expression, activating MAPK and PI3K/AKT pathways.
  • MIR503HG overexpression suppressed tumor growth in vivo.

Conclusions:

  • MIR503HG functions as a tumor suppressor long non-coding RNA (lncRNA) in ovarian cancer.
  • MIR503HG exerts its tumor-suppressive effects by inhibiting the SPI1-TMEFF1 axis.
  • MIR503HG represents a potential therapeutic target for ovarian cancer treatment.
Keywords:
MIR503HGSPI1TMEFF1ovarian cancer

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