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

26 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 - 2014 Sep 1

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Autophagy
MicroRNAs
Hepatocellular Carcinoma
Carcinogenesis
Amiodarone
Off-Label Use
Neoplasms
Hepatitis B virus
Confocal Microscopy
Cell Movement
In Situ Hybridization
Electron Microscopy
Gene Expression
Autophagosomes
Therapeutics

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Lan, S. H., Wu, S. Y., Zuchini, R., Lin, X. Z., Su, I. J., Tsai, T. F., ... 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
Lan, Sheng Hui ; Wu, Shan Ying ; Zuchini, Roberto ; Lin, Xi Zhang ; Su, Ih Jen ; Tsai, Ting Fen ; Lin, Yen Ju ; Wu, Cheng Tao ; Liu, Hsiao Sheng. / Autophagy-preferential degradation of MIR224 participates in hepatocellular carcinoma tumorigenesis. In: Autophagy. 2014 ; Vol. 10, No. 9. pp. 1687-1689.
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Lan, SH, Wu, SY, Zuchini, R, Lin, XZ, Su, IJ, Tsai, TF, Lin, YJ, Wu, CT & Liu, HS 2014, 'Autophagy-preferential degradation of MIR224 participates in hepatocellular carcinoma tumorigenesis', Autophagy, vol. 10, no. 9, pp. 1687-1689. https://doi.org/10.4161/auto.29959

Autophagy-preferential degradation of MIR224 participates in hepatocellular carcinoma tumorigenesis. / Lan, Sheng Hui; Wu, Shan Ying; Zuchini, Roberto; Lin, Xi Zhang; Su, Ih Jen; Tsai, Ting Fen; Lin, Yen Ju; Wu, Cheng Tao; Liu, Hsiao Sheng.

In: Autophagy, Vol. 10, No. 9, 01.09.2014, p. 1687-1689.

Research output: Contribution to journalArticle

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AU - Wu, Shan Ying

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AU - Tsai, Ting Fen

AU - Lin, Yen Ju

AU - Wu, Cheng Tao

AU - Liu, Hsiao Sheng

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