The Role And Molecular Mechanism Of ARHGEF3 Gene In The Development Of Non-small Cell Lung Cancer

ARHGEF3 is a guanine nucleotide exchange factor(GEF),belonging to DbI family proteins.GEF proteins regulate the activation of Rho family proteins,which involved in numerous cell processes such as cytoskeleton organization,gene transcription,cell proliferation and migration.However,the studies on the function of ARHGEF3 are relatively few.Recent studies demonstrated that ARHGEF3 protein mainly possessed two functional mechanisms: the first function was that it activated RhoA and RhoB proteins as a GEF;besides,it could also function as an endogenous inhibitor of mTORC2.However,little is known about the function of ARHGEF3 in cancer.It was reported that ARHGEF3 protein could regulate the differentiation of lymphoma cells into macrophages induced by deacetylase inhibitors.In addition,the antisense chain of ARHGEF3 gene could transcribe a long non-coding RNAARHGEF3-AS1 and the function of this lncRNA was unclear.The purpose of this study was to investigate the function and mechanism of ARHGEF3 gene in non-small cell lung cancer.We found that ARHGEF3 protein and ARHGEF3-AS1 are highly expressed in non-small cell lung cancer cells.Knocking down of ARHGEF3 protein by specific siRNA significantly inhibited the growth and migration of H1299 cells and A549 cells,and inhibited the cell cycle in the G0/G1 phase,Further studies have shown that ARHGEF3 protein affects Cyclin D1 transcription by regulating the NF-kappaB signaling pathway,thus affecting cell cycle transport.ARHGEF3-AS1 could also promote the growth of H1299 cells.These results demonstrated that ARHGEF3 could regulate the proliferation of NSCLC cells though regulating cell cycle progression.