miR-634 activates the mitochondrial apoptosis pathway and enhances chemotherapy-induced cytotoxicity

Naoto Fujiwara, Jun Inoue, Tatsuyuki Kawano, Kousuke Tanimoto, Ken Ichi Kozaki, Johji Inazawa

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31 Citations (Scopus)

Abstract

Some tumor-suppressing miRNAs target multiple oncogenes concurrently and therefore may be useful as cancer therapeutic agents. Further, such miRNAs may be useful to address chemotherapeutic resistance in cancer, which remains a primary clinical challenge in need of solutions. Thus, cytoprotective processes upregulated in cancer cells that are resistant to chemotherapy are a logical target for investigation. Here, we report that overexpression of miR-634 activates the mitochondrial apoptotic pathway by direct concurrent targeting of genes associated with mitochondrial homeostasis, antiapoptosis, antioxidant ability, and autophagy. In particular, we show how enforced expression of miR-634 enhanced chemotherapyinduced cytotoxicity in a model of esophageal squamous cell carcinoma, where resistance to chemotherapy remains clinically problematic. Our findings illustrate how reversing miR-634-mediated cytoprotective processes may offer a broadly useful approach to improving cancer therapy.

Original languageEnglish
Pages (from-to)3890-3901
Number of pages12
JournalCancer Research
Volume75
Issue number18
DOIs
Publication statusPublished - Sep 15 2015

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Fujiwara, N., Inoue, J., Kawano, T., Tanimoto, K., Kozaki, K. I., & Inazawa, J. (2015). miR-634 activates the mitochondrial apoptosis pathway and enhances chemotherapy-induced cytotoxicity. Cancer Research, 75(18), 3890-3901. https://doi.org/10.1158/0008-5472.CAN-15-0257