N6-methyladenosine modified LINC00901 promotes pancreatic cancer progression through IGF2BP2/MYC axis

Accumulating evidence indicates that RNA methylation at N6-methyladenosine(m6A)plays an important regulatory role in gene expression and aberrant mRNA m6A modification is often associated with a variety of cancers.However,little is known whether and how m6A-modification impacts long non-coding RNA(lncRNA)and lncRNA-mediated tumorigenesis,particularly in pancreatic ductal adenocarcinoma(PDAC).In the present study,we report that a previously uncharacterized lncRNA,LINC00901,promotes pancreatic cancer cell growth and invasion and moreover,LINC00901 is subject to m6A modification which regulates its expression.In this regard,YTHDF1 serves as a reader for the m6A modified LINC00901 and downregulates the LINC00901 level.Notably,two conserved m6A sites in LINC00901 are critical to the recognition of LINC00901 by YTHDF1.Finally,RNA sequencing(RNA-seq)and gene function analysis revealed that LINC00901 positively regulates MYC through upregulation of IGF2BP2,a known RNA binding protein that can enhance MYC mRNA stability.Together,our results suggest that there is a LINC00901-IGF2BP2-MYC axis through which LINC00901 promotes PDAC progression in an m6A dependent manner.