Transcription factors NFIA and NFIB induce cellular differentiation in high-grade astrocytoma

• DOI: 10.1007/s11060-019-03352-3
• Publication Date: 2019-11-23T08:02:37Z
• Authors: Kok-Siong Chen; Caitlin R. Bridges; Zorana Lynton; Jonathan W. C. Lim; Brett W. Stringer; Revathi Rajagopal; Kum-Thong Wong; Dharmendra Ganesan; Hany Ariffin; Bryan W. Day; Linda J. Richards; Jens Bunt
• Keywords: 0301 basic medicine; Cancer Research; Neurogenesis; Clinical Neurology; 610; Apoptosis; Mice, SCID; Mice; 03 medical and health sciences; Mice, Inbred NOD; Biomarkers, Tumor; Tumor Cells, Cultured; Animals; Humans; 1306 Cancer Research; Cell Proliferation; 0303 health sciences; Cell Differentiation; Xenograft Model Antitumor Assays; 3. Good health; Gene Expression Regulation, Neoplastic; NFI Transcription Factors; Oncology; Neurology; 2808 Neurology; 2730 Oncology; 2728 Clinical Neurology; Neoplasm Grading; Glioblastoma

AbstractAstrocytomas are composed of heterogeneous cell populations. Compared to grade IV glioblastoma, low-grade astrocytomas have more differentiated cells and are associated with a better prognosis. Therefore, inducing cellular differentiation may serve as a therapeutic strategy. The nuclear factor one (NFI) transcription factors are essential for normal astrocytic differentiation and therefore could be effectors of cellular differentiation in glioblastoma. We analysed expression of family membersNFIAandNFIBusing high-grade astrocytoma mRNA expression datasets, and with immunofluorescence co-staining. Their expression is reduced in glioblastomas and is associated with differentiated and mature astrocyte-like cells at a cellular level. Furthermore, induction of NFI expression is sufficient to promote cellular differentiation in patient-derived glioblastoma xenografts. Our findings indicate that NFI proteins may have an endogenous pro-differentiative function in astrocytomas, similar to their role in normal development. Overall, our study establishes a basis for further investigation of targeting NFI-mediated differentiation as a potential differentiation therapy.