Identification of MYEOV-Associated Gene Network as a Potential Therapeutic Target in Pancreatic Cancer

SIMPLE SUMMARY: Exploring the key molecular regulatory mechanism of pancreatic cancer is crucial to investigate the therapeutic strategies for pancreatic cancer. To precisely identify key pancreatic cancer genes, we used a multiple analyses integrated approach. We performed gene association analysis on the key gene MYEOV we discovered, which led to a molecular network with MYEOV as the core. The genes in this molecular network could work together to influence the development of pancreatic cancer, possibly through protumor immune cell infiltration. It is the first report to focus on the possibility that MYEOV may act as a ceRNA to form an interaction network with some pancreatic cancer-related genes such as KRAS and serve as a strategic therapeutic target of pancreatic cancer treatment. ABSTRACT: The molecular mechanism that promotes pancreatic cancer remains unclear, so it is important to find the molecular network of important genes related to pancreatic cancer. To find the key molecule of pancreatic cancer, differential gene expression analyses were analyzed by the Deseq2 package, edgeR package, and limma-voom package, respectively. Pancreatic cancer survival-related genes were analyzed by COX survival analysis. Finally, we integrated the results to obtain the significantly differentially expressed gene, MYEOV (myeloma overexpressed gene), most strongly related to survival in pancreatic cancer. Experimental verification by qRT-PCR confirmed that transcription levels of MYEOV mRNA markedly increased in pancreatic cancer cells relative to normal human pancreatic ductal epithelial cells (HPDE). Through the comprehensive analysis of multiple databases, we constructed a molecular network centered on MYEOV and found specific links between molecules in this network and tumor-associated immune cells. It was noted that MYEOV could serve as a ceRNA by producing molecular sponging effects on hsa-miR-103a-3p and hsa-miR-107, thus affecting the role of GPRC5A, SERPINB5, EGFR, KRAS, EIF4G2, and PDCD4 on pancreatic cancer progression. Besides, we also identified that infiltrated immune cells are potential mediators for the molecules in the MYEOV-related network to promote pancreatic cancer progression. It is the first report to focus on the possibility that MYEOV may act as a competing endogenous RNA (ceRNA) to form an interactive network with some pancreatic cancer-related genes such as KRAS and serve as a key therapeutic target of pancreatic cancer treatment.