Oncotarget

Research Papers:

BMI-1 is a potential therapeutic target in diffuse intrinsic pontine glioma

Shiva Senthil Kumar, Satarupa Sengupta, Kyungwoo Lee, Nanki Hura, Christine Fuller, Mariko DeWire, Charles B. Stevenson, Maryam Fouladi, Rachid Drissi _

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Abstract

Shiva Senthil Kumar1,*, Satarupa Sengupta1,*, Kyungwoo Lee1,*, Nanki Hura1, Christine Fuller2, Mariko DeWire1, Charles B. Stevenson3, Maryam Fouladi1 and Rachid Drissi1

1Brain Tumor Center, Division of Oncology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

2Division of Pathology and Laboratory Medicine, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

3Division of Pediatric Neurosurgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA

*These authors contributed equally to this work

Correspondence to:

Rachid Drissi, email: rachid.drissi@cchmc.org

Keywords: DIPG, BMI-1, cell proliferation, cancer stem cells, therapeutic target

Received: April 02, 2017    Accepted: April 26, 2017    Published: May 19, 2017

ABSTRACT

Diffuse intrinsic pontine glioma (DIPG) is a poor-prognosis pediatric brain tumor. No effective curative therapy is currently available and no therapeutic advances have been made in several decades. BMI-1 is a member of the multimeric protein complex Polycomb repressor complex 1. It is highly expressed in a number of diseases and malignancies and has been implicated in self-renewal of normal and cancer cells, and in DNA damage signaling. The role of BMI-1 in DIPG is largely unknown. Here, we show that BMI-1 is highly expressed in tumor tissue samples of DIPG patients and in patient-derived cancer stem-like cells. BMI-1 downregulation leads to the inhibition of DIPG patient-derived neurosphere cell proliferation, cell cycle signaling, self-renewal, telomerase expression and activity, and suppresses DIPG cell migration. Moreover, targeted inhibition of BMI-1 sensitizes DIPG cells to radiomimetic drug-induced DNA damage. Together, our data validate BMI-1 as a potential therapeutic target to treat children with DIPG.

Author Information

Shiva Senthil Kumar

Satarupa Sengupta

Kyungwoo Lee

Nanki Hura

Christine Fuller

Mariko DeWire

Charles B. Stevenson

Maryam Fouladi

Rachid Drissi
Primary Contact  _


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