Long Noncoding RNA LIPE-AS1 Drives Prostate Cancer Progression by Functioning as a Competing Endogenous RNA for microRNA-654-3p and Thereby Upregulating Hepatoma-Derived Growth Factor

Abstract

Information regarding the expression and roles of LIPE antisense RNA 1 (LIPE-AS1) in prostate cancer (PCa) progression is currently limited. We experimentally determined LIPE-AS1 expression in PCa tissues and cell lines. The specific functions of LIPE-AS1 in the oncogenicity of PCa were explored by evaluating a series of cellular functions. Moreover, the molecular mechanisms underlying the oncogenic roles of LIPE-AS1 in PCa were investigated. The expression level of LIPE-AS1 was determined via quantitative reverse transcription polymerase chain reaction. Functional experiments, including the Cell Counting Kit-8 assay, Transwell migration and invasion assays, and tumor xenograft experiments, were used to determine the effects of LIPE-AS1 on PCa cells. The putative miRNA-binding LIPE-AS1 was predicted via bioinformatics analysis and further verified using the luciferase reporter and RNA immunoprecipitation assays. LIPE-AS1 was expressed at high levels in PCa cells; this result is consistent with that of The Cancer Genome Atlas database. Patients with PCa manifesting high LIPE-AS1 expression had shorter overall survival than those manifesting low LIPE-AS1 expression. Downregulated LIPE-AS1 inhibited PCa cell proliferation, migration, and invasion in vitro and impaired tumor growth in vivo. With respect to its mechanism, LIPE-AS1 functioned as a competing endogenous RNA for microRNA-654-3p (miR-654-3p) in PCa cells, and hepatoma-derived growth factor (HDGF) was the direct target of miR-654-3p. HDGF was positively regulated by LIPE-AS1 in PCa cells via the absorption of miR-654-3p. Rescue experiments confirmed that miR-654-3p downregulation or HDGF overexpression counteracts the inhibitory effects of LIPE-AS1 depletion on PCa cell proliferation, migration, and invasion. LIPE-AS1 promotes PCa malignancy by targeting the miR-654-3p/HDGF axis. Determining the LIPE-AS1/miR-654-3p/HDGF pathway may increase our understanding of PCa pathogenesis and contribute toward a wider applied scope.