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

Research output: Contribution to journalArticle

25 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

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Apoptosis
Drug Therapy
Neoplasms
MicroRNAs
Gene Targeting
Autophagy
Oncogenes
Homeostasis
Antioxidants
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

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

miR-634 activates the mitochondrial apoptosis pathway and enhances chemotherapy-induced cytotoxicity. / Fujiwara, Naoto; Inoue, Jun; Kawano, Tatsuyuki; Tanimoto, Kousuke; Kozaki, Ken Ichi; Inazawa, Johji.

In: Cancer Research, Vol. 75, No. 18, 15.09.2015, p. 3890-3901.

Research output: Contribution to journalArticle

Fujiwara, N, Inoue, J, Kawano, T, Tanimoto, K, Kozaki, KI & Inazawa, J 2015, 'miR-634 activates the mitochondrial apoptosis pathway and enhances chemotherapy-induced cytotoxicity', Cancer Research, vol. 75, no. 18, pp. 3890-3901. https://doi.org/10.1158/0008-5472.CAN-15-0257
Fujiwara, Naoto ; Inoue, Jun ; Kawano, Tatsuyuki ; Tanimoto, Kousuke ; Kozaki, Ken Ichi ; Inazawa, Johji. / miR-634 activates the mitochondrial apoptosis pathway and enhances chemotherapy-induced cytotoxicity. In: Cancer Research. 2015 ; Vol. 75, No. 18. pp. 3890-3901.
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