AFF1-the Component Of Super Elongation Complex Regulate Chemokines In Lung Cancer

Abstract:Transcription plays a vital role in development and the pathogenesis.In eukaryotes,RNA polymerase ? is responsible for the synthesis of mRNA,Pol ?transcription initiation is dependent on binding with a variety of general transcription factors(GTF).After GTF and Pol ? form the preinitiation complex,the positive transcription factor(p-TEFb)phosphorylats poised Pol ?,bring the process into an elongation stage.This procedure is called transcriptional elongation checkpoint control(TECC)Recruitment of the super elongation complex(SEC)is the key step of TECC.SEC usually consists of the eleven-nineteen Lys-rich leukaemia(ELL)family proteins(RNA polymerase ? elongation factors),positive transcription elongation factor b(P-TEFb)and several frequent mixed lineage leukaemia(MLL)translocation partners,such as AFF1,AFF4,ENL and AF9.The SEC family members function diversely during development and cancer pathogenesis.It has been reported that AFF1,the core component of SEC,is involved in the occurrence of acute leukemia,However,the function of AFFl in solid tumors remains unknown.Our studies demonstrate that AFF1,the core component of SEC,is associated with non-small cell lung cancer.The further research using RNA interference reveals that AFF1 can regulate the gene expression of CXC family.The transcriptions of several CXC chemokines,such as CXCL1,CXCL3,and CXCL5,was significantly reduced after AFF1 knockdown.Combine with ChIP-Seq data,we found that AFF1 binding on the CXC gene body and the pattern of pol ? is identical to TECC.In addition to AFF1,other components of SEC also bind to the CXC locus.This suggests that the regulation of CXC family by AFF1 depends on the recruitment of SEC.Our study reveals a role of AFF1 in solid tumor and lays a foundation for the treatment of non-small cell lung cancer.