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Identification of pyruvate kinase type M2 as potential oncoprotein in squamous cell carcinoma of tongue through

Thian-Sze Wong1, Xiao-Bing Liu1, Ambrose Chung-Wai Ho1

  • 1Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

International Journal of Cancer
|May 9, 2008
PubMed

Insights

Reduced miR-133a and miR-133b levels are linked to tongue squamous cell carcinoma (SCC) progression. Restoring these microRNAs (miRNAs) inhibits SCC cell proliferation and increases apoptosis by targeting PKM2.

Area of Science:

  • Molecular Biology
  • Oncology
  • Gene Regulation

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression implicated in various cancers.
  • The role of miRNAs in tongue squamous cell carcinoma (SCC) remains largely unexplored.
  • Understanding miRNA dysregulation is crucial for identifying novel therapeutic targets in tongue SCC.

Purpose of the Study:

  • To investigate the expression patterns of miRNAs in tongue SCC.
  • To determine the functional impact of specific miRNAs on SCC cell behavior.
  • To identify the molecular targets of dysregulated miRNAs in tongue SCC.

Main Methods:

  • Taqman-based microRNA assays were used to profile 156 mature miRNAs in tongue SCC tissues and paired normal cells.
  • Functional assays, including proliferation and apoptosis studies, were performed on SCC cell lines transfected with miRNA precursors.
  • Computational target prediction and immunohistochemical staining were employed to validate miRNA-target interactions.

Main Results:

  • miR-133a and miR-133b were significantly downregulated in tongue SCC compared to normal epithelium.
  • Overexpression of miR-133a and miR-133b precursors reduced SCC cell proliferation and induced apoptosis.
  • Pyruvate kinase type M2 (PKM2) was identified as a direct target of miR-133a and miR-133b, with its expression reduced upon miRNA precursor transfection.
  • PKM2 was found to be overexpressed in tongue SCC tissues, correlating with decreased miR-133a and miR-133b levels.

Conclusions:

  • Aberrant downregulation of miR-133a and miR-133b is a notable feature of tongue SCC.
  • These miRNAs play a tumor-suppressive role in tongue SCC by inhibiting proliferation and promoting apoptosis.
  • The dysregulation of the miR-133a/miR-133b-PKM2 axis contributes to the pathogenesis of tongue SCC.

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