Abstract 3868: The stem cell factor LIN28B regulates proliferation and apoptosis in diffuse intrinsic pontine glioma

Abstract

Diffuse Intrinsic Pontine Glioma (DIPG) is an incurable, invasive and aggressive pediatric brain tumor. Identifying molecular markers that regulate tumor growth and invasion are needed for developing efficient treatment strategies. LIN28B is a stem cell factor expressed during normal fetal development and re-expressed in cancer cells. We had previously shown that LIN28A, another family member of LIN28 proteins, regulates invasion and tumorigenicity in adult high grade gliomas. We observed increased LIN28B expression in patient-derived DIPG neurosphere cell lines using western blotting. We hypothesized that LIN28B promotes proliferation and prevents apoptosis in DIPG. Using two different lentiviral transduced short hairpin RNAs (shRNA), we suppressed LIN28B protein levels in DIPG neurospheres, as confirmed by western blotting. DIPG neurospheres that have been treated with LIN28B shRNA showed reduced proliferation as measured by BrdU incorporation (P<0.01) and increased apoptosis as measured by cleaved caspase-3 (CC-3) expression (P<0.01). To determine the molecular mechanism of LIN28B-mediated phenotypes in DIPG, we studied the canonical downstream effector of LIN28B called HMGA2, which is a DNA-binding protein that functions as a transcriptional regulator. Using western blotting, we found decreased HMGA2 protein levels in DIPG neurospheres infected with LIN28B shRNA. Taken together, our results suggest that LIN28B is important for promoting DIPG cell proliferation and preventing apoptotic cell death. Additionally, we also found that LIN28B regulates HMGA2 expression in DIPG neurospheres. Future studies will focus on expanding our understanding of the molecular mechanisms of LIN28B-regulated malignancy in DIPG. Citation Format: Huizi Guo, Sepehr Akhtarkhavari, Charles G. Eberhart, Harpreet Kaur, Eric H. Raabe. The stem cell factor LIN28B regulates proliferation and apoptosis in diffuse intrinsic pontine glioma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3868. doi:10.1158/1538-7445.AM2017-3868