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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
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microRNA-129-5p, a c-Myc negative target, affects hepatocellular carcinoma progression by blocking the Warburg effect

Han Han1, Wenjuan Li1, Hongxing Shen1

  • 1College of Life Sciences, Medical Research Institute, Wuhan University, Wuhan 430072, China.

Journal of Molecular Cell Biology
|March 23, 2016
PubMed

Insights

MicroRNAs (miRNAs) and c-Myc (Myc) are implicated in liver cancer. This study reveals miR-129-5p inhibits hepatocellular carcinoma (HCC) by targeting PDK4, thus blocking glycolysis and tumor growth.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Dysregulation of microRNAs (miRNAs) and c-Myc (Myc) is common in hepatocellular carcinoma (HCC).
  • The intricate relationship between miRNAs and Myc in hepatocarcinogenesis remains largely unexplored.

Purpose of the Study:

  • To elucidate the role of miR-129-5p in HCC progression.
  • To investigate the regulatory mechanisms between miRNAs and Myc in liver cancer.
  • To identify potential therapeutic targets for HCC.

Main Methods:

  • Functional screening to identify HCC-inhibiting miRNAs.
  • Luciferase reporter assays and Western blotting to confirm target interactions.
  • In vivo mouse models (diethylnitrosamine-induced hepatocarcinogenesis) and cell-based assays.

Main Results:

  • miR-129-5p was identified as a tumor suppressor in HCC, targeting pyruvate dehydrogenase kinase 4 (PDK4).
  • miR-129-5p inhibits glycolysis, reduces tumor growth, and impairs lung metastasis by downregulating PDK4.
  • Myc, in complex with HDAC3 and EZH2, transcriptionally represses miR-129-5p.
  • miR-129-5p levels inversely correlate with HCC clinical stage, and its restoration suppresses DEN-induced hepatocarcinogenesis in mice.

Conclusions:

  • miR-129-5p acts as a tumor suppressor in HCC by targeting PDK4 and inhibiting glycolysis.
  • Myc represses miR-129-5p, establishing a critical regulatory axis in hepatocarcinogenesis.
  • The miR-129-5p/PDK4 pathway represents a promising therapeutic target for HCC.
Keywords:
PDK4c-Mychepatocellular carcinomamicroRNAthe Warburg effect

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