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MicroRNA-99a/100 promotes apoptosis by targeting mTOR in human esophageal squamous cell carcinoma

Jian Sun1, Zhaoli Chen, Xiaogang Tan

  • 1Department of Thoracic Surgery, Cancer Hospital and Institute, Chinese Academy of Medical Sciences, Beijing 100021, People's Republic of China.

Medical Oncology (Northwood, London, England)
|January 8, 2013
PubMed

Insights

MicroRNA-99a and microRNA-100 (miR-99a/100) are downregulated in esophageal squamous cell carcinoma (ESCC). Restoring miR-99a/100 levels inhibits ESCC cell proliferation by targeting mTOR, suggesting a potential therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • MicroRNA-99 family members (miR-99a/b, miR-100) show altered expression in cancers, but their role in carcinomas is debated.
  • Esophageal squamous cell carcinoma (ESCC) is a significant global health concern with limited therapeutic options.

Purpose of the Study:

  • To investigate the function and mechanism of miR-99a and miR-100 in ESCC.
  • To determine if miR-99a/100 can serve as a therapeutic target for ESCC.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) to assess miR-99a/100 expression in ESCC tissues and cell lines.
  • Transfection of miR-99a/100 precursor molecules to study effects on cell proliferation and apoptosis.
  • Luciferase reporter assays and Western blots to elucidate the molecular mechanism involving mTOR.

Main Results:

  • miR-99a and miR-100 were significantly downregulated in ESCC tissues and cell lines.
  • Overexpression of miR-99a/100 inhibited ESCC cell proliferation and induced apoptosis.
  • miR-99a/100 directly targeted the 3' untranslated region (3'UTR) of mTOR, suppressing its expression post-transcriptionally.
  • Lower miR-99a/100 expression correlated with poorer overall survival in ESCC patients.

Conclusions:

  • miR-99a and miR-100 function as tumor suppressors in ESCC by inhibiting cell proliferation via mTOR suppression.
  • The miR-99a/100-mTOR signaling pathway represents a promising therapeutic target for ESCC treatment.

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