Long non-coding RNA UCA1 regulates MPP+-induced neuronal damage through the miR-671-5p/KPNA4 pathway in SK-N-SH cells

• Published in: Metabolic brain disease Vol. 38; no. 3; pp. 961 - 972
• Main Authors: Hao, Zhengheng, Dang, Wen, Zhu, Qingfeng, Xu, Jianxing
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.03.2023; Springer Nature B.V
• Subjects: 1-Methyl-4-phenylpyridinium - toxicity; Age; alpha Karyopherins; Apoptosis; Assaying; Biochemistry; Biomedical and Life Sciences; Biomedicine; Bladder cancer; Carcinoma, Transitional Cell; Cell Line, Tumor; Cell viability; Damage; Enzyme-linked immunosorbent assay; Flow cytometry; Functional analysis; Humans; Immunoprecipitation; Inflammation; L-Lactate dehydrogenase; Lactate dehydrogenase; Metabolic Diseases; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Movement disorders; MPP; mRNA; Neurodegenerative Diseases; Neurology; Neurosciences; Non-coding RNA; Oncology; Original Article; Oxidative stress; Parkinson Disease - genetics; Parkinson's disease; Pathogenesis; Polymerase chain reaction; Ribonucleic acid; RNA; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Superoxide dismutase; Time dependence; Urinary Bladder Neoplasms; Urothelial carcinoma; Western blotting; UCA1; KPNA4; PD; miR-671-5p; MPP; Neuronal
• ISSN: 0885-7490; 1573-7365
• DOI: 10.1007/s11011-022-01118-x

Parkinson’s disease (PD) is an age-related neurodegenerative disease. Long non-coding RNA urothelial carcinoma-associated 1 (UCA1) is involved in the pathogenesis of PD. However, the pathogenesis of PD regulated by UCA1 has not been fully explained. We used 1-Methyl-4-phenylpyridinium (MPP + )-induced SK-N-SH cells for functional analysis. Expression levels of UCA1, microRNA (miR)-671-5p, and KPNA4 (karyopherin subunit alpha 4) mRNA were detected using quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were analyzed using MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) or flow cytometry assays. Some protein levels were measured by western blotting. The levels of pro-inflammatory cytokines were tested by ELISA (enzyme-linked immunosorbent assay). The levels of LDH (lactate dehydrogenase), MDA (malondialdehyde), and SOD (superoxide dismutase) were measured using corresponding kits. The relationship between UCA1 or KPNA4 and miR-671-5p was verified by dual-luciferase reporter assay and/or RNA immunoprecipitation (RIP) assay. MPP + induced UCA1 expression in SK-N-SH cells in a concentration-dependent manner or time-dependent manner. UCA1 knockdown reduced MPP + -induced apoptosis, inflammation, and oxidative stress in SK-N-SH cells. MiR-671-5p was downregulated while KPNA4 was upregulated in MPP + -treated SK-N-SH cells. UCA1 sponged miR-671-5p to regulate KPNA4 expression. MiR-671-5p inhibition counteracted UCA1 knockdown-mediated influence on apoptosis, inflammation, and oxidative stress of MPP + -induced SK-N-SH cells. KPNA4 overexpression offset the inhibitory influence of miR-671-5p mimic on apoptosis, inflammation, and oxidative stress of MPP + -treated SK-N-SH cells. UCA1 inhibition reduced MPP + -induced neuronal damage through the miR-671-5p/KPNA4 pathway in SK-N-SH cells, providing a novel mechanism to understand the pathogenesis of PD.