Parkinson’s disease-related lncRNA PINK1-AS advances glioma oncogenesis by activating IPO5-RAS signaling pathway

Abstract Background: Epidemiological studies have demonstrated a higher incidence of gliomas in patients with Parkinson's disease. However, the underlying molecular mechanisms remain unclear, and insights into why and how patients with Parkinson's disease are susceptible to gliomas are essential for advancing novel therapeutic approaches for both diseases. Methods: The Chinese Glioma Genome Atlas (CGGA) database was used to screen Parkinson’s disease-related genes associated with glioma prognosis. The expression of the lncRNA PINK1-AS in the brain tissue of patients with Parkinson’s diseaseand glioma tissues and cells was characterized by quantitative reverse transcription polymerase chain reaction. The efficacy of PINK1-AS knockdown in gliomas was evaluated by assessing cell proliferation, migration, cell cycles, and experimental xenografts. To establish the relationship between the PINK1-AS, miR-200a-3p, and IPO5 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 brain tissue of patients with Parkinson’s disease, 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 malignant phenotypes, including cell promotion, metastasis, and aggression in vitro and xenograft tumor generation in vivo. Furthermore, PINK1-AS may serve as a pool for miR-200a-3p, thereby de-repressing IPO5 and activating the RAS signaling pathway. Conclusions: PINK1-AS, highly expressed in both Parkinson's disease and glioma, regulates IPO5 expression by downregulating miR-200a-3p and activating the RAS signaling pathway.