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Repression of the long noncoding RNA-LET by histone deacetylase 3 contributes to hypoxia-mediated metastasis

Fu Yang1, Xi-song Huo, Sheng-xian Yuan

  • 1Department of Medical Genetics, Second Military Medical University, Shanghai, 200433, China.

Molecular Cell
|February 12, 2013
PubMed

Insights

Hypoxia represses long noncoding RNA-LET (lncRNA-LET) expression in cancers via histone deacetylase 3. This downregulation promotes cancer cell invasion and metastasis, offering potential therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Long noncoding RNAs (lncRNAs) are increasingly recognized for their roles in cancer.
  • The precise molecular mechanisms controlling lncRNA expression in tumors are not fully understood.

Purpose of the Study:

  • To investigate the regulatory mechanisms of lncRNA expression in cancer.
  • To elucidate the role of lncRNA-LET in cancer progression, particularly in response to hypoxia.

Main Methods:

  • Quantitative analysis of lncRNA-LET expression in tumor samples.
  • Investigation of the role of histone deacetylase 3 (HDAC3) and histone acetylation in lncRNA-LET regulation.
  • Assessment of the impact of lncRNA-LET downregulation on cancer cell invasion and nuclear factor 90 (NF90) protein stability.

Main Results:

  • lncRNA-LET was found to be significantly downregulated in hepatocellular carcinoma, colorectal cancer, and lung cancer.
  • Hypoxia-induced HDAC3 was shown to repress lncRNA-LET by reducing histone acetylation at its promoter.
  • Downregulation of lncRNA-LET stabilized NF90 protein, promoting hypoxia-induced cancer cell invasion.
  • A correlation between hypoxia, histone acetylation disorder, low lncRNA-LET levels, and metastasis was observed in clinical hepatocellular carcinoma samples.

Conclusions:

  • Hypoxia-driven epigenetic dysregulation, involving HDAC3 and histone acetylation, leads to decreased lncRNA-LET expression.
  • lncRNA-LET acts as a crucial suppressor of cancer cell invasion and metastasis by modulating NF90 stability.
  • These findings highlight lncRNA-LET as a potential therapeutic target for inhibiting cancer progression in hypoxic environments.

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