Long noncoding RNA DIO3OS interacts with miR-122 to promote proliferation and invasion of pancreatic cancer cells through upregulating ALDOA

Abstract

BackgroundLong noncoding RNA (lncRNA) has been implicated in numerous tumors, including pancreatic cancer (PC). However, the precise cellular roles and molecular mechanisms of lncRNA DIO3OS on PC development remains to be fully clarified.MethodsWe performed the meta-analysis on PC samples and non-tumor samples retrieved from the TCGA database, and measured the levels of DIO3OS in PC cell lines and a normal pancreatic duct epithelial cell line HPDE6-C7. Cell proliferation was evaluated via CCK-8 assay. Cell invasion in vitro was investigated by transwell assay. The RNA immunoprecipitation assay and luciferase reporter assay was utilized to confirm the putative miR-122-binding site in DIO3OS. The effects of DIO3OS on PC progression were tested using in vivo subcutaneous xenografts.ResultsOur results showed that DIO3OS was highly expressed in human PC tissues and PC cell lines. DIO3OS exhibited oncogenic properties in stimulating PC cell proliferation and invasion in vitro and promoting cancer growth in vivo. Through online predictive tools and functional experiments, we found that DIO3OS could bind directly to microRNA-122 (miR-122) and inhibited its expression, which functioned as a tumor suppressor in PC cells. We also verified that ALDOA was the direct target of miR-122, and the tumor suppressive effects caused by DIO3OS knockdown or miR-122 overexpression could be rescued by re-expression of ALDOA in PC cells.ConclusionsOverall, our study suggested that lncRNA DIO3OS promotes PC cell growth and invasion by competing for miR-122 to modulate the expression of ALDOA. These findings yield a better understanding of the potential mechanisms by which gain of DIO3OS expression accelerates PC progression.