BMI-1 is a potential therapeutic target in diffuse intrinsic pontine glioma
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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
Rachid Drissi, email: [email protected]
Keywords: DIPG, BMI-1, cell proliferation, cancer stem cells, therapeutic target
Received: April 02, 2017 Accepted: April 26, 2017 Published: May 19, 2017
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.
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