Long non-coding RNA myocardial infarction-associated transcript promotes 1-Methyl-4-phenylpyridinium ion-induced neuronal inflammation and oxidative stress in Parkinson’s disease through regulating microRNA-221-3p/ transforming growth factor /nuclear factor E2-related factor 2 axis

Abstract

This study attempted to evaluate the role of long non-coding RNA myocardial infarction-associated transcript (LncRNA MIAT) in Parkinson’s disease (PD). The mouse model was established through intraperitoneal injection with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and in vitro model was induced by administrating cell with 1-Methyl-4-phenylpyridinium ion (MPP + ). Rotarod test was conducted to evaluate the motor coordination of PD mice. In order to investigate the roles of LncRNA MIAT in neuronal inflammation and oxidative stress, MIAT shRNA (shMIAT) was transfected into MPP + -treated cells, and cell viability, cell apoptosis and oxidative stress response were evaluated. To evaluate the interactions between LncRNA MIAT and microRNA-221-3p (miR-221-3p)/TGF-β1/Nrf2, miR-221-3p mimic, miR-221-3p inhibitor, NC-inhibitor and transforming growth factor-β1 shRNA (shTGF-β1) were subsequently transfected into MPP+-treated cells. Dual-luciferase reporter gene assays were performed to determine the interaction of miR-221-3p with MIAT or TGFB receptor 1 (TGFBR1). The expressions of LncRNA MIAT, miR-221-3p, TGFBR1, transforming growth factor (TGF-β1) and nuclear factor E2-related factor 2 (Nrf2) were measured by quantitative reverse-transcription polymerase chain reaction (RT-qPCR) and immunoblotting. As a result, LncRNA MIAT was abundantly expressed in PD mice and cells, while downregulation of LncRNA MIAT promoted the survival of neurons, inhibited apoptosis and oxidative stress in neurons. LncRNA MIAT bound to miR-221-3p, and there was a negative correlation between miR-221-3p and LncRNA MIAT expression. In addition, miR-221-3p targeted TGFBR1 and suppressed TGF-β1 expression but increased Nrf2 expression. LncRNA MIAT promoted MPP + -induced neuronal injury in PD via regulating TGF-β1/Nrf2 axis through binding with miR-221-3p.

Crosstalk between regulatory non-coding RNAs and oxidative stress in Parkinson’s disease

“…Among the 17 newly studied lncRNAs, 13 were identified to aggravate oxidative stress and inflammatory responses in neurons, namely AL049437, HOTAIR, LINC00943, lncRNA-p21 (lnc-p21), MIAT, NEAT1, rhabdomyosarcoma 2-associate transcript (RMST), SNHG1, SNHG7, SOS1 intronic transcript 1 (SOS1-IT1), SRY-box transcription factor 2 overlapping transcript (SOX2-OT), taurine upregulated gene 1 (TUG1), and UCA1 (Cai et al, 2019 ; Ding et al, 2019 ; Zhai et al, 2020 ; Zhang L. et al, 2020 ; Zhao et al, 2020b ; Guo et al, 2021 ; Lian et al, 2021 ; Ma et al, 2021a ; Zhang et al, 2021 ; Zhou S. et al, 2021 ; Fan et al, 2022 ; Lang et al, 2022 ). The other four lncRNAs, namely JHDM1D antisense 1 (JHDM1D-AS1), myocardial infarction associated transcript 2 (Mirt2), small nucleolar RNA host gene 12 (SNHG12), and PART1, exhibited anti-oxidant and anti-inflammatory roles in models of PD, as evidenced by the decline in proinflammatory cytokines and increase in SOD contents (Han et al, 2019 ; Shen et al, 2021b ; Wang C. et al, 2021 ; Yan et al, 2021 ).…”

Regulation of Oxidative Stress by Long Non-coding RNAs in Central Nervous System Disorders

“…Blocking MIAT increases cell viability and inhibits cell apoptosis. Additionally, MIAT enhances Nrf2 expression by modulating its target, miR-221-3p ( Lang et al, 2022 ).…”

MicroRNAs in the epigenetic regulation of disease progression in Parkinson’s disease

“…But studies are sparse on the role of miRNAs in regulating TGF-β1 in PD. Interestingly, a study by Lang et al (2022) investigated the interactions between LncRNA MIAT and miR-221-3p regulated TGF-β1/Nrf2. The study employed the use of a miR-221-3p mimic, a miR-221-3p inhibitor, an NC-inhibitor, and a shRNA (shTGF-β1) which were transfected into MPP+treated cells.…”

“…Furthermore, miR-221-3p inhibited TGF-β1 expression while increasing Nrf2 expression. MIAT, a LncRNA, enhanced MPP+induced neuronal damage in PD through modulating the TGF-β1/Nrf2 axis by interaction with miR-221-3p (Lang et al, 2022).…”