Preliminary Study On The Function And Mechanism Of NXPH4 In Glioblastoma

Neurexophilin4(NXPH4)is a 29 k D.neuronal synapse secretory protein,belonging to the Neurexophilin(NXPH)family whose family member was first considered to be a neuroglycoprotein abundantly expressed in the nervous system and named after tightly binding to Neurexin Iα.It has been found that NXPH4 is highly expressed in glioma,liver cancer,non-small cell lung cancer,colorectal cancer,breast cancer,and many other cancer cells.The phenotype is particularly obvious in glioma,so we decide to explore the function and mechanism of NXPH4 in glioma.Glioma is the most common primary brain tumor in the central nervous system,and glioblastoma multiforme(GBM)is one of the most malignant brain tumor,with high invasiveness and high fatality rate.The prognosis is poor,and the patient’s survival period is generally only 12-15 months.The current main treatments include surgical resection,radiotherapy and chemotherapy,and immunotherapy.The development of glioma is a very complex biological process,including changes at the molecular and cellular levels.Some current clinical drugs,such as temozolomide,bevacizumab,etc.,have poor effect in patients due to individual differences.Therefore,only a comprehensive and profound understanding of the pathogenesis of gliomas can be targeted to create better treatment.In this experiment,data analysis by bioinformatics methods found that NXPH4 which is induced by hypoxia is not only highly expressed in glioma cells,but also highly expressed in clinical tissue samples of various grades of glioma,and the expression level of NXPH4 is negatively correlated with patient survival and prognosis;According to the expression level of the glioma cell line,the U251/A172 cell line was selected to construct the NXPH4 knockdown cell line.Growth curve and Brd U incorporation assay proved that the proliferation of glioma cells was significantly inhibited after knocking down the expression of NXPH4 protein.Transwell and cell scratching results proved the migration ability was also inhibited in NXPH4 knockdown cells.We then analyzed with bioinformatics methods and found that the proliferation and migration inhibition of NXPH4 knockdown cells may caused by preventing cell cycle progression and reducing cell self-renewal ability.Flow cytometry and tumor sphere formation experiments proved that the cell cycle is blocked in G0/G1 phaseand its cell self-renewal ability is inhibited after knocking down NXPH4,.The molecular mechanism study is still on the way.In summary,NXPH4 plays important role in glioblstoma by regulating cell proliferation and migration and may serve as prognosis biomarker or therapeutic target in the future.