Expression of far upstream element (FUSE) binding protein 1 in human glioma is correlated with c‐Myc and cell proliferation

Abstract

Glioma is one of the most common type of primary intracranial tumor. Although great advances have been achieved in treatment of glioma, the underlying molecular mechanisms remain largely unknown. Previous studies demonstrated that FBP1 is a transcriptional regulator of c-Myc and acts as an important prognostic indicator in many cancers. Our study aimed to assess the expression and function of FBP1 in human glioma. Immunohistochemical and Western blot analysis were performed in human glioma and normal brain tissues. High FBP1 expression (located in cell nuclei) was observed in 70 samples and its level was correlated with the grade of malignancy. A strongly positive correlation was observed between FBP1 and c-Myc (P = 0.005) and Ki-67 expression (P = 0.009). In a multivariate analysis, high FBP1 and c-Myc expressions were showed to be associated with poor prognosis in glioma. While in vitro, following serum stimulation of starved U87MG cells, the expression of FBP1 was upregulated, as well as c-Myc and PCNA. Moreover, knockdown of FBP1 by siRNA transfection diminished the expression of c-Myc and arrested cell growth at G1 phase. Collectively, our results shows that the expression of FBP1 is in close correlation with c-Myc level and cell proliferation in glioma and provides a potential strategy to develop FBP1 inhibitors as novel anti-tumor agents.

Far Upstream Element Binding Protein Plays a Crucial Role in Embryonic Development, Hematopoiesis, and Stabilizing Myc Expression Levels

“…The hypercellularity of the brain in the absence of FBP is in accord with its identification as a tumor suppressor in oligodendrogliomas, but it contrasts with the association of FBP with higher levels of MYC, proliferation, and worse prognosis in gliomas. 28 Across different embryonic tissues at different developmental stages, FBP function seems to be contextual, suggesting that it adjusts rather than defines biological state.…”

The Splicing Factor FUBP1 Is Required for the Efficient Splicing of Oncogene MDM2 Pre-mRNA

“…FUBP1 is single strand DNA and RNA-binding protein best known for its role as a transcriptional regulator of the proto-oncogene c-MYC in many cancer types (31,32,50,51) and also as regulator of post-transcriptional events such as translation (38) and mRNA stability (23). However, despite the fact that FUBP1 has been isolated in association with spliceosomal complexes (40) and includes four K homology domains (domains homologous to heterogeneous nuclear ribonucleoprotein K, a component of the spliceosomal H complexes (52)), its role in splicing regulation has remained speculative until recently.…”

“…Regardless of the role it plays, FUBP1 is an important modifier of crucial tumor-suppressive and oncogenic programs within the cell. In this respect, it has been shown to function through both c-MYC-dependent and -independent pathways as a regulator of transcriptional and post-transcriptional events such as pre-mRNA translation (23,25,36,38,50,51,56,57). For instance, FUBP1 has inextricable ties with the p53 tumor-suppressor pathway through its transcriptional control of far upstream element-containing genes c-MYC and USP29 and also via its regulation of translation and stability of nucleophosmin and p21 mRNA (23,38,56,57).…”

Overexpression of CCT8 and its significance for tumor cell proliferation, migration and invasion in glioma

“…The negative control siRNA was also designed by Biomics Biotechnologies Co., Ltd. (China). Cell transfection was as described previously [9].…”