Parkinson’s disease-related lncRNA PINK1-AS advances glioma oncogenesis by regulating the YAP1-Hippo signaling pathway

Abstract

Abstract Background Epidemiological studies have demonstrated a higher incidence of gliomas in patients with Parkinson’s disease (PD). However, the underlying molecular mechanisms remain unclear, and insights into why and how patients with PD are susceptible to glioma are essential for advancing novel therapeutic approaches for both diseases. Therefore, we investigate the function of PD-related lncRNA PINK1-AS in glioma progression.Methods The expression of the long non-coding PTEN-induced kinase 1 antisense RNA gene (PINK1-AS) in PD and glioma tissues and cells was characterized by quantitative reverse transcription polymerase chain reaction. The efficacy of PINK1-AS knockdown in glioma cell lines was evaluated by assessing cell proliferation, migration, and cell cycles. In addition, experimental xenografts were administered to nude mice to evaluate the effect of PINK1-AS on gliomas. To establish the relationship between the PINK1-AS, miR-200a, and yes-associated protein 1 (YAP1) genes, RNA immunoprecipitation, RNA probe pull-down, luciferase reporter, and fluorescence in situ hybridization assays were performed.Results PINK1-AS expression was anomalously elevated in PD, glioma tissues, and cell lines compared to normal brain tissue, and the overall survival time was reduced in patients with glioma with high PINK1-AS expression. PINK1-AS knockdown remarkably suppressed glioma metaplasia, including cell promotion, metastasis, and aggression in vitro and xenograft tumor generation in vivo. Furthermore, PINK1-AS targeted miR-200a, and miR-200a inhibition inverted the virulent features of PINK1-AS knockdown on glioma cells. Specifically, PINK1-AS may serve as a competing endogenous RNA that effectively functions as a pool for miR-200a, thereby de-repressing YAP1.Conclusions PINK1-AS is a key inhibitor of the Hippo signaling pathway by inhibiting miR-200a, and targeting PINK1-AS may be a novel therapeutic strategy for patients with glioma, especially those with PD.