Ninj2 Reduces GBM Proliferation Through Intracellular Calcium

Glioblastoma multiforme GBM is a kind of malignant brain tumor,which is differentiated from astrocytes.It has the characteristics of rapid development and high degree of malignancy.Also,It is very difficult to be cure.Current researches focus on the changes of signal pathway about GBM.In this study,we investigated the effect of a membrane adhesion molecule,Ninjurin2(Ninj2),on tumor development.Ninjurin2 is a member of the Ninjurin family.It has been reported to play an important role in the process of nerve injury and regeneration.Previously,we found that abnormal expression of Ninj2 in tumor cell line can reduce tumorigenesis in vivo.Through in vitro experiments,we find that overexpression of Ninj2 significantly reduce cell viability in the GBM cell line U87-MG,At the same time,Knocking down Ninj2 promotes cell proliferation.However,we find that the abnormal expression of Ninj2 in U87-MG does not affect cell migration and apoptosis.By analyzing the RNA-seq data of U87-MG that overexpressing Ninj2,we notice that the genes involved in cell cycle regulation are significantly changed.Cell cycle Flow cytometry also proves that overexpressing Ninj2 can induce G1 arrest.In contrast,knocking-down of Ninj2 will promotes the cell cycle transition from G1 to S phase.By measuring intracellular calcium concentration,we found that overexpression of Ninj2 in U87-MG reduces the intracellular calcium content,and knocking down of Ninj2 can increase the total calcium content.By using the calcium chelation EGTA to reduce extracellular calcium concentration,we found that calcium can affect the cell cycle arrest caused by abnormal expression of Ninj2.Also,calcium can affect the expression of cyclin D which is associated with G1 phase.In our study,We first discover the tumor suppressing effect of Ninj2 in GBM,After that,we have reported its regulation mechanism of cell cycle transformation through calcium.Ninj2 can be defined as a new GBM research direction.We are looking forward to providing more valuable reference for the treatment of GBM.