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Tumor and Stem Cell Biology

miR-182-5p Induced by STAT3 Activation Promotes Glioma Tumorigenesis

Jianfei Xue, Aidong Zhou, Yamei Wu, Saint-Aaron Morris, Kangyu Lin, Samirkumar Amin, Roeland Verhaak, Gregory Fuller, Keping Xie, Amy B. Heimberger and Suyun Huang
Jianfei Xue
Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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Aidong Zhou
Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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Yamei Wu
Department of Hematology, The First Affiliated Hospital, Chinese PLA General Hospital, Beijing, China.
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Saint-Aaron Morris
Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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Kangyu Lin
Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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Samirkumar Amin
Department of Genomic Medicine; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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Roeland Verhaak
Department of Genomic Medicine; Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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Gregory Fuller
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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Keping Xie
Department of Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas.Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas.
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Amy B. Heimberger
Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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Suyun Huang
Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas.
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  • For correspondence: suhuang@mdanderson.org
DOI: 10.1158/0008-5472.CAN-15-3073
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Abstract

Malignant glioma is an often fatal type of cancer. Aberrant activation of STAT3 leads to glioma tumorigenesis. STAT3-induced transcription of protein-coding genes has been extensively studied; however, little is known about STAT3-regulated miRNA gene transcription in glioma tumorigenesis. In this study, we found that abnormal activation or decreased expression of STAT3 promotes or inhibits the expression of miR-182-5p, respectively. Bioinformatics analyses determined that tumor suppressor protocadherin-8 (PCDH8) is a candidate target gene of miR-182-5p. miR-182-5p negatively regulated PCDH8 expression by directly targeting its 3′-untranslated region. PCDH8 knockdown induced the proliferative and invasive capacities of glioma cells. Silencing of PCDH8 or miR-182-5p mimics could reverse the inhibitory effect of WP1066, a STAT3 inhibitor, or STAT3 knockdown in vitro and in vivo on glioma progression. Clinically, expression levels of PCDH8 were inversely correlated with those of p-STAT3 or miR-182-5p in glioblastoma tissues. These findings reveal that the STAT3/miR-182-5p/PCDH8 axis has a critical role in glioma tumorigenesis and that targeting the axis may provide a new therapeutic approach for human glioma. Cancer Res; 76(14); 1–12. ©2016 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).

  • Received November 10, 2015.
  • Revision received March 30, 2016.
  • Accepted April 23, 2016.
  • ©2016 American Association for Cancer Research.
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Published OnlineFirst July 5, 2016
doi: 10.1158/0008-5472.CAN-15-3073

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miR-182-5p Induced by STAT3 Activation Promotes Glioma Tumorigenesis
Jianfei Xue, Aidong Zhou, Yamei Wu, Saint-Aaron Morris, Kangyu Lin, Samirkumar Amin, Roeland Verhaak, Gregory Fuller, Keping Xie, Amy B. Heimberger and Suyun Huang
Cancer Res July 5 2016 DOI: 10.1158/0008-5472.CAN-15-3073

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miR-182-5p Induced by STAT3 Activation Promotes Glioma Tumorigenesis
Jianfei Xue, Aidong Zhou, Yamei Wu, Saint-Aaron Morris, Kangyu Lin, Samirkumar Amin, Roeland Verhaak, Gregory Fuller, Keping Xie, Amy B. Heimberger and Suyun Huang
Cancer Res July 5 2016 DOI: 10.1158/0008-5472.CAN-15-3073
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