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

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

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Introduction: Malignant astrocytomas 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 to alter the behaviour of high-grade astrocytomas may serve as a therapeutic strategy. The nuclear factor one (NFI) transcription factors are essential for normal astrocytic differentiation. Here, we investigate whether family members NFIA and NFIB act as effectors of cellular differentiation in glioblastoma. Methods: We analysed expression of NFIA and NFIB in mRNA expression data of high-grade astrocytoma and with immunofluorescence co-staining. Furthermore, we induced NFI expression in patient-derived subcutaneous glioblastoma xenografts via in vivo electroporation. Results: The expression of NFIA and NFIB is reduced in glioblastoma as compared to lower grade astrocytomas. At a cellular level, their expression is associated with differentiated and mature astrocyte-like tumour cells. In vivo analyses consistently demonstrate that expression of either NFIA or NFIB is sufficient to promote tumour cell differentiation in glioblastoma xenografts. Conclusion: Our findings indicate that both NFIA and NFIB may have an endogenous pro-differentiative function in astrocytomas, similar to their role in normal astrocyte differentiation. Overall, our study establishes a basis for further investigation of targeting NFI-mediated differentiation as a potential differentiation therapy.

Original languageEnglish
Pages (from-to)41-53
Number of pages13
JournalJournal of Neuro-Oncology
Volume146
Issue number1
DOIs
StatePublished - Jan 1 2020

Keywords

  • Astrocytoma
  • Differentiation
  • Glioblastoma
  • NFIA
  • NFIB
  • Nuclear factor I

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