Downregulation of the microRNA biogenesis components and its association with poor prognosis in hepatocellular

Noriyuki Kitagawa1, Hidenori Ojima, Takuya Shirakihara

  • 1Division of Cancer Genomics, National Cancer Center Research Institute, Tokyo, Japan.

Cancer Science
|February 13, 2013
PubMed

Insights

Deregulation of microRNA (miRNA) biogenesis genes is common in non-viral hepatocellular carcinoma (HCC). Reduced expression of these genes correlates with risk factors, multicentric tumors, and poor HCC prognosis, suggesting epigenetic links.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Genetic alterations in miRNA biogenesis are implicated in human cancers.
  • Dicer gene deletion promotes carcinogenesis in animal models, highlighting miRNA's role in cancer.
  • Aberrant miRNA biogenesis components are linked to cancer development.

Purpose of the Study:

  • To investigate the expression of miRNA biogenesis pathway genes in hepatocellular carcinoma (HCC).
  • To correlate gene expression with HCC subtypes, risk factors, tumor characteristics, and patient prognosis.
  • To explore the role of epigenetic regulation in miRNA biogenesis gene deregulation in HCC.

Main Methods:

  • Quantitative RT-PCR was used to analyze the expression of 14 miRNA biogenesis genes.
  • 47 paired samples of primary HCC and matched non-cancerous liver tissue were analyzed.
  • Histone modification analysis (H3K27 trimethylation) was performed on HCC cell lines.

Main Results:

  • Seven miRNA biogenesis genes showed decreased expression in HCC, particularly in non-viral HCC.
  • Reduced expression correlated with risk factors (smoking, alcohol, diabetes), multicentric tumors, and poor prognosis (Dicer, p68).
  • Epigenetic regulation via histone H3 lysine 27 trimethylation was implicated in gene deregulation in non-HBV HCC cell lines.

Conclusions:

  • Deregulation of miRNA biogenesis pathway components is frequent in non-viral HCC.
  • This deregulation is associated with etiological risk factors and predicts a poor prognosis.
  • Epigenetic mechanisms, such as histone modifications, contribute to miRNA biogenesis gene deregulation during hepatocarcinogenesis.

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