Rasip1 Is A RUNX1b Target Gene And Promotes Migration Of NSCLC Cell

Runt-related transcription factor 1b(RUNX1b),an essential reg?Lator of hematopoiesis,is overexpressed in patients with non-small cell lung cancer(NSCLC)and is correlated with enhanced metastatic ability.Ras-interacting protein 1(Rasipl),a potential oncogene,is required for blood vessel formation,and elevated expression of Rasipl in NSCLC patients has been shown recently.We noticed that Rasip1 promoter contains several potential RUNX1b-binding sequences.However,the relationship between Rasipl and RUNX1b in NSCLC is still unknown.Here,we detected that RUNX1b was the main variant in adenocarcinoma cancer of NSCLC.Ectopic expression or knockdown of RUNX1b res?Lted in a significant increase or reduction of Rasip1 expression,respectively.RUNX1b bound directly to a specific DNA sequence within Rasip1 promoter and mod?Lated its transcription.Moreover,serine 249 of RUNX1b was phosphorylated after epidermal growth factor(EGF)stim?Lation and the mutation of this site abolished its transcription function.Furthermore,silencing of Rasip1 inhibited the migration of RUNX1b-overexpressing NSCLC cell.In addition,we found that Rasipl was expressed ubiquitously in NSCLC cell lines,and enhanced cell migration through activation of Racl and ERK pathway.Taken together,our data indicated that Rasip1 is reg?Lated in part by the transcription factor RUNX1b and might be developed as a therapeutic target for NSCLC.