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

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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

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leukemia
Tumors
Leukemia
Cells
Apoptosis Regulatory Proteins
neoplasms
cell lines
Hematopoietic Stem Cells
Cell Line
stem cells
Neoplasms
apoptosis
Apoptosis
14-3-3 Proteins
Cell growth
Hematologic Neoplasms
Stem cells
MicroRNAs
microRNA
cell viability

All Science Journal Classification (ASJC) codes

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

Cite this

Scheibner, K. A., Teaboldt, B., Hauer, M. C., Chen, X., Cherukuri, S., Guo, Y., ... 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
Scheibner, Kara A. ; Teaboldt, Brianne ; Hauer, Mary Claire ; Chen, Xiaochun ; Cherukuri, Srujana ; Guo, Yin ; Kelley, Shannon M. ; Liu, Zhenqiu ; Baer, Maria R. ; Heimfeld, Shelly ; Civin, Curt I. / MiR-27a Functions as a Tumor Suppressor in Acute Leukemia by Regulating 14-3-3θ. In: PloS one. 2012 ; Vol. 7, No. 12.
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Scheibner, KA, Teaboldt, B, Hauer, MC, Chen, X, Cherukuri, S, Guo, Y, Kelley, SM, Liu, Z, Baer, MR, Heimfeld, S & Civin, CI 2012, 'MiR-27a Functions as a Tumor Suppressor in Acute Leukemia by Regulating 14-3-3θ', PloS one, vol. 7, no. 12, e50895. https://doi.org/10.1371/journal.pone.0050895

MiR-27a Functions as a Tumor Suppressor in Acute Leukemia by Regulating 14-3-3θ. / Scheibner, Kara A.; Teaboldt, Brianne; Hauer, Mary Claire; Chen, Xiaochun; Cherukuri, Srujana; Guo, Yin; Kelley, Shannon M.; Liu, Zhenqiu; Baer, Maria R.; Heimfeld, Shelly; Civin, Curt I.

In: PloS one, Vol. 7, No. 12, e50895, 07.12.2012.

Research output: Contribution to journalArticle

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AU - Scheibner, Kara A.

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AU - Civin, Curt I.

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Scheibner KA, Teaboldt B, Hauer MC, Chen X, Cherukuri S, Guo Y et al. MiR-27a Functions as a Tumor Suppressor in Acute Leukemia by Regulating 14-3-3θ. PloS one. 2012 Dec 7;7(12). e50895. https://doi.org/10.1371/journal.pone.0050895