Abstract
RAN binding protein 10 (RANBP10), a ubiquitously expressed and evolutionarily conserved protein, as a RAN-GTP exchange factor (GEF) to regulate several factors involved in cellular progression. Previous studies showed that RANBP10 was overexpressed in prostate cancer cells and was responsible for androgen receptor (AR) activation. However, the biological function of RANBP10 in glioblastoma (GBM) has not been studied. Here, we found that RANBP10 was overexpressed in GBM, and high RANBP10 expression was closely linked to poor survival of patients with GBM. Downregulation of RANBP10 significantly inhibited cell proliferation, migration, invasion, and tumor growth of GBM cells. In addition, we revealed that RANBP10 could suppress the promoter activity of FBXW7, and thereby increase the protein stability of c-Myc in GBM cells. Silencing of FBXW7 in RANBP10-knockdown GBM cells could partly negate the effects induced by RANBP10 downregulation. Taken together, our findings established that RANBP10 significantly promoted GBM progression by control of the FBXW7–c-Myc axis, and suggest that RANBP10 may be a potential target in GBM.
Highlights
Diffuse gliomas, a heterogeneous group of central nervous tumors, are characterized by rapid proliferation, intensive infiltration, and resistance to treatment
RAN binding protein 10 (RANBP10) was highly expressed in Glioblastoma multiforme (GBM) and was associated with poor prognosis of GBM patients Overexpression of RANBP10 was found in several cancer types, including brain and CNS cancer, gastric cancer, kidney cancer, and prostate cancer (Supplementary Fig. S1A)
These results demonstrated that RANBP10 was highly expressed in GBM and high RANBP10 expression was associated with a poor prognosis of GBM patients
Summary
A heterogeneous group of central nervous tumors, are characterized by rapid proliferation, intensive infiltration, and resistance to treatment. RANBP10 exerts important functions by interacting with several proteins, such as MET, RAN, YPEL5 (Yippee like 5), Protein Kinase C (PKC), and β1-tubulin [8,9,10,11]. Recent studies have demonstrated that RANBP10 played important roles in the cell cycle, spindle assembly, the reproductive system, and tumor progression [8, 10, 13, 14]. In ARpositive prostate cancer cells, RANBP10 was highly expressed and was responsible for the activation of AR, thereby contributed to prostate cancer development and progression [13]. RANBP10 might function in the DNA Damage Response (DDR) of cancer cells due to the post-translational modification following genotoxic stress [7]. The biological function of RANBP10 in tumors, especially in GBM has not been studied
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
