Kinesin family protein 2A (KIF2A), an M-type nonmotile microtubule depolymerase, plays essential roles in development and progression of various human cancers. However, its exact function and the underlying mechanism in tumorigenesis of gastric cancer (GC) haven't been fully elucidated. In the present study, KIF2A was overexpressed in human GC and predicted poor prognosis according to the results of GEPIA analysis. KIF2A was also observed to be upregulated in 82 GC samples compared with paired pericarcinoma tissues. Its overexpression was associated with tumor metastasis (P = 0.047) and Ⅲ stage GC (P = 0.0267). The mRNA and protein expression levels of KIF2A were significantly suppressed in KIF2A specific siRNA transfected GC cells compared with the wild-type and negative control (NC) siRNA transfected cells. Furthermore, the effects of KIF2A on the growth, migration, invasion, and apoptosis of GC cell were evaluated in vitro and the underlying mechanisms were explored. It was found that silencing KIF2A effectively induced the apoptosis, and inhibited the proliferation, migration and invasion capacities of GC cells. Western blot analysis demonstrated that silencing of KIF2A significantly decreased the expression levels of AKT, Cyclin D1 and S6K. Moreover, bioinformatics analysis showed that the promoter (from -414 to -407bp) of KIF2A has the ability to bind to transcription factor ETV4, which was confirmed by bi-luciferase reporter assay using 293T cells. The level of ETV4 was upregulated and positively correlated with KIF2A in human GC tissues. Our results also proved that ETV4 upregulated the expression of KIF2A and blocked the decline of proliferation induced by KIF2A knockdown in MKN-45 and AGS cells. In summary, KIF2A is upregulated by transcription factor ETV4, and its knockdown can effectively inhibit the proliferation and induce the apoptosis of GC cells through the AKT signaling pathway in GC cells, implying that the inhibition of KIF2A expression is a potential target for GC therapy.
Keywords: Apoptosis; ETV4; Gastric cancer; Growth; KIF2A; Prognosis.
Copyright © 2020. Published by Elsevier Masson SAS.