MiR-27a Functions as a Tumor Suppressor in Acute Leukemia by Regulating 14-3-3θ

Kara A. Scheibner, Brianne Teaboldt, Mary Claire Hauer, Xiaochun Chen, Srujana Cherukuri, Yin Guo, Shannon M. Kelley, Zhenqiu Liu, Maria R. Baer, Shelly Heimfeld, Curt I. Civin

Research output: Contribution to journalArticle

Abstract

MicroRNAs (miRs) play major roles in normal hematopoietic differentiation and hematopoietic malignancies. In this work, we report that miR-27a, and its coordinately expressed cluster (miR-23a~miR-27a~miR-24-2), was down-regulated in acute leukemia cell lines and primary samples compared to hematopoietic stem-progenitor cells (HSPCs). Decreased miR-23a cluster expression in some acute leukemia cell lines was mediated by c-MYC. Replacement of miR-27a in acute leukemia cell lines inhibited cell growth due, at least in part, to increased cellular apoptosis. We identified a member of the anti-apoptotic 14-3-3 family of proteins, which support cell survival by interacting with and negatively regulating pro-apoptotic proteins such as Bax and Bad, as a target of miR-27a. Specifically, miR-27a regulated 14-3-3θ at both the mRNA and protein levels. These data indicate that miR-27a contributes a tumor suppressor-like activity in acute leukemia cells via regulation of apoptosis, and that miR-27a and 14-3-3θ may be potential therapeutic targets.

Original languageEnglish (US)
Article numbere50895
JournalPLoS One
Volume7
Issue number12
DOIs
StatePublished - Dec 7 2012
Externally publishedYes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Scheibner, K. A., Teaboldt, B., Hauer, M. C., Chen, X., Cherukuri, S., Guo, Y., Kelley, S. M., Liu, Z., Baer, M. R., Heimfeld, S., & Civin, C. I. (2012). MiR-27a Functions as a Tumor Suppressor in Acute Leukemia by Regulating 14-3-3θ. PLoS One, 7(12), [e50895]. https://doi.org/10.1371/journal.pone.0050895