microRNA expression changes after knocking out MYEOV in two human pancreatic cancer cell lines

Pancreatic cancer (PC) remains a highly lethal malignancy worldwide. As metastasis and malignant proliferation are primarily responsible for poor clinical outcomes of PC, it is imminent to dig out the pivotal gene involved in the process as well as its underlying molecular mechanism. In this study, through analysis of TCGA and GTEx data, we found that the expression level of MYEOV was obviously increased in carcinoma tissues relative to healthy ones and associated with poor survival in PC patients. The elevated abundance of MYEOV was positively correlated with enhanced cell proliferation, invasion and migration in vivo and in vitro. The global transcriptome analysis of MYEOV-depleted PC cells revealed the downregulation of various genes involved in active cell proliferation, which indicated that MYEOV overexpression was critical for PC progression. MiRNA-seq analysis showed that MYEOV had a regulatory effect on the expression levels of miR-17-5p and miR-93-5p, depletion of which resulted in reduced cell proliferation, invasion and migration as observed in MYEOV-knockdown PC cells. Such effect was imposed by MYEOV through affecting enrichment of the transcription factor c-myc at the gene promoter regions of the two miRNAs. Furthermore, a complex containing MYEOV and MYC was confirmed to exist in cell nucleus, providing convictive evidence for the association of MYEOV with MYC. Together, these results suggested that the axis of MYEOV-MYC-miR-17/93-5p could be vital for PC progression and could act as a potential therapeutic target to interrupt cell proliferation which will benefit treatment and management of PC patients. Overall design: small RNAs after knocking out MYEOV in two human pancreatic cancer cell lines were isolated and sequenced by deep sequencing using Illumina HiSeq 4000 from novogene.