Roles Of SNAI2—E-cadherin Axis In The Regulation Of Invasion And Metastasis Of Glioma Cells By LRIG1

Objective To investigate the effects and mechanisms of leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1)in invasion and metastasis of U251 cells and the effects of SNAI2 and E-cadherin in these process during the invasion and metastasis of gliomas. To reveal the changes in the ability of invasion and metastasis of U251 cells when LRIGl is upregulated by employing plasmid carrying LRIGl gene or down-regulated by employing siRNA that can slient LRIG1 specifically. To reveal the potential mechanisms that the SNAI2—E-cadherin axis may have participated in regulating the invasion and metastasis of gliomas at the same time.Methods U251 cells were cultured and randomly divided into three groups: control group, PEGFP-N1-LRIG1 group and PEGFP-LRIG1-U251 group, which were respectively transfected with PBS?PEGFP-N1 plasmid and PEGFP-LRIG1 plasmid by liposome transfection. siLRIG1 was performed to knock down the expressions of LRIG1,besides that, Si-NC and blank control group were employed as controls. The specimens of human gliomas and normal brain tissues were collected to detect the protein expression of LRIG1, SNAI2 and E-cadherin. LRIG1 knocked down U251 cells by siLRIG1 was treated by PCPA, a small molecular inhibitor of SNAI2, to reveal the role of SNAI2 in the process of LRIG1 regulates the invasion and metastasis of gliomas. The expression changes of LRIG1,SNAI2 and E-cadherin were detected by real time-PCR and Western blotting. The invasion of each group cells were assayed by transwell chamber assay. The metastasis of each group cells were detected by transwell chamber assay with a matrigel coating and wound healing test.Results LRIG1 gene was transfected into PEGFP-LRIG1-U251 cells and were knocked down in Si-LRIG1-U251 cells. LRIG1 overexpression inhibited cell invasion and metastasis coupled with reduced SNAI2 expression and raised E-cadherin expression. By contrast, knockdown of endogenous LRIG1 promoted cell invasion and metastasis coupled with reduced E-cadherin expression and raised SNAI2 expression. Compared to normal brain tissues, the expression of LRIG1 and E-cadherin protein was much lower in human gliomas, and SNAI2 was much higher in human gliomas.The small molecular inhibitor PCPA can inhibite SNAI2 and reverse the effects of lower level LRIG1 on the invasion and metastasis of gliomas.Conclusion LRIG1 can inhibite the invasion and metastasis of human glioma cells. It's potential molecular mechanisms may be that LRIG1 can suppress the SNAI2-—E-cadherin axis, leading to the reducing of cell movement and cytomorphosis and inhibite the invasion and metastasis of human glioma cells finally. The expression of LRIG1 and E-cadherin protein was much lower and SNAI2 was much higher in human gliomas than normal brain tissues And further study is needed to reveal the molecular mechanisms in detail how LRIG1 regulate the invasion and metastasis of gliomas through SNAI2—E-cadherin axis.