Long non-coding RNA nuclear enriched abundant transcript 1 (NEAT1) sponges microRNA-124-3p to up-regulate phosphodiesterase 4B (PDE4B) to accelerate the progression of Parkinson's disease.

Reportedly, long non-coding RNA (lncRNA) are crucial modulators in neurodegenerative diseases. Herein, we investigated the role of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in Parkinson's disease (PD). In-vitro PD model was established based on SH-SY5Y cells treated with 1-methyl-4-phenylpyridinium (MPP+). NEAT1, microRNA (miR) -124-3p and phosphodiesterase 4B (PDE4B) expression levels were examined by qRT-PCR. CCK-8 assay and LDH release assay were adopted to delve into the cell viability and cytotoxicity, respectively. Besides, western blot was utilized to determine mTOR, p-mTOR and PDE4B expression levels. ELISA was executed to detect the levels of tumor necrosis factor α (TNF-α), interleukin 1ß (IL-1ß) and interleukin 6 (IL-6). Dual-luciferase reporter assay and RIP assay were used to probe the relationship between miR-124-3p and NEAT1 or PDE4B. We demonstrated that, in SH-SY5Y cells treated with MPP+, NEAT1 and PDE4B expression levels were raised, while miR-124-3p expression was repressed; NEAT1 depletion or miR-124-3p overexpression increased the cell viability and suppressed cell injury. Besides, miR-124-3p was confirmed as the direct target of NEAT1, and its down-regulation counteracted the impact of NEAT1 depletion on SH-SY5Y cells. PDE4B was as the downstream target of miR-124-3p, and its overexpression weakens the impact of miR-124-3p on SH-SY5Y cells. Additionally, NEAT1 decoyed miR-124-3p to modulate PDE4B expression. Collectively, in MPP+-induced SH-SY5Y cells, NEAT1 depletion increases cell viability, represses cytotoxicity and reduces inflammatory response by regulating miR-124-3p and PDE4B expression levels, suggesting that NEAT1 may be a promising target for treating PD.

Long non-coding RNA-p21 regulates MPP+-induced neuronal injury by targeting miR-625 and derepressing TRPM2 in SH-SY5Y cells.

Parkinson's disease (PD), the second most prevalent age-related neurodegenerative disease, occurs as a result of the loss of dopaminergic neurons in the substantia nigra. Long non-coding RNA-p21 (lnc-p21) has been demonstrated to be upregulated in PD. However, its role in PD is unknown. Here, the results showed that lnc-p21 was highly expressed in human neuroblastoma SH-SY5Y cells treated with MPP+. Knockdown of lnc-p21 attenuated the cytotoxicity and cell apoptosis induced by MPP+ as shown by enhanced cell viability, decreased LDH release and cell apoptosis rate, accompanying with reduction of caspase-3 activity and Bax expression, and enhancement of Bcl-2 expression. Furthermore, knockdown of lnc-p21 mitigated MPP+-induced oxidative stress and neuroinflammation, as evidenced by the decrease in ROS generation, increase in SOD activity and decline in TNF-α, IL-1ß and IL-6 levels. Conversely, overexpression of lnc-p21 resulted in the opposite effect. miR-625 was identified as a target of lnc-p21. lnc-p21 overturned the inhibitory effect of miR-625 on MPP+-induced neuronal injury in SH-SY5Y cells. Additionally, lnc-p21 positively regulated TRPM2 expression by targeting miR-625, and knockdown of TRPM2 inhibited MPP+-induced neuronal injury. Overall, our study identified a new lnc-p21-miR-625-TRPM2 regulatory network that lnc-p21 regulated MPP + -induced neuronal injury by sponging miR-625 and upregulating TRPM2 in SH-SY5Y cells, which provide a better understanding for the pathogenesis of PD.