Autophagy-preferential degradation of MIR224 participates in hepatocellular carcinoma tumorigenesis

Sheng Hui Lan, Shan Ying Wu, Roberto Zuchini, Xi Zhang Lin, Ih Jen Su, Ting Fen Tsai, Yen Ju Lin, Cheng Tao Wu, Hsiao Sheng Liu

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Autophagy and microRNA (miRNA) are important regulators during cancer cell tumorigenesis. Impaired autophagy and high expression of the oncogenic microRNA MIR224 are prevalent in hepatocellular carcinoma (HCC); however, the relationship between the 2 phenomena remains elusive. In this study, we are the first to reveal that autophagy selectively regulates MIR224 expression through an autophagosome-mediated degradation system. Based on this finding, we further demonstrated that in hepatitis B virus (HBV)-related HCC, aberrant autophagy (low autophagic activity) results in accumulation of MIR224 and decreased expression of the target gene Smad4, which leads to increased cell migration and tumor formation. Preferential recruitment of MIR224 into the autophagosome was clearly demonstrated by a) miRNA in situ hybridization under confocal microscopy, and b) immunogold labeling of MIR224 under electron microscopy compared with a ubiquitously expressed microRNA MIRlet7e/let-7. Furthermore, we found that off-label use of amiodarone, an antiarrhythmic agent, effectively suppressed HCC tumorigenesis through autophagy-mediated MIR224 degradation both in vitro and in vivo. In summary, we identified amiodarone as a new autophagy inducer, which may provide an alternative approach in HCC therapy through a novel tumor suppression mechanism.

Original languageEnglish
Pages (from-to)1687-1689
Number of pages3
JournalAutophagy
Volume10
Issue number9
DOIs
Publication statusPublished - Sep 1 2014

Keywords

  • Autophagy
  • HBV
  • HCC
  • MiR-224
  • MiRNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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  • Cite this

    Lan, S. H., Wu, S. Y., Zuchini, R., Lin, X. Z., Su, I. J., Tsai, T. F., Lin, Y. J., Wu, C. T., & Liu, H. S. (2014). Autophagy-preferential degradation of MIR224 participates in hepatocellular carcinoma tumorigenesis. Autophagy, 10(9), 1687-1689. https://doi.org/10.4161/auto.29959