Long non‐coding RNA MALAT1 regulates cell proliferation and apoptosis via miR-135b-5p/GPNMB axis in Parkinson’s disease cell model

Abstract

Backgrounds Parkinson’s disease (PD) is a common age-related neurodegenerative disorder worldwide. This research aimed to investigate the effects and mechanism underlying long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in PD. Methods SK-N-SH and SK-N-BE cells were treated with MPP+ to establish the MPP+-stimulated cell model of PD, and MALAT1 expression was determined. Then, the effects of MALAT1 depletion on cell proliferation and apoptosis were determined in the MPP+-stimulated cell model of PD. Besides, the correlations between microRNA-135b-5p (miR-135b-5p) and MALAT1 or glycoprotein nonmetastatic melanoma protein B (GPNMB) in MPP+-stimulated cell model of PD were explored. Results MALAT1 was increasingly expressed and downregulation of MALAT1 promoted cell proliferation while inhibited apoptosis in MPP+-stimulated cells. Besides, miR-135b-5p was a target of MALAT1 and directly targeted to GPNMB. Further investigation indicated that suppression of MALAT1 regulated cell proliferation and apoptosis by miR-135b-5p/GPNMB axis. Conclusion Our findings reveal that MALAT1/miR-135b-5p/GPNMB axis regulated cell proliferation and apoptosis in MPP+-stimulated cell model of PD, providing a potential biomarker and therapeutic target for PD.

Significant role of long non-coding RNA MALAT1 in deep vein thrombosis via the regulation of vascular endothelial cell physiology through the microRNA-383-5p/BCL2L11 axis

“…LncRNAs can directly interact with miRNAs as competitive endogenous RNAs, thereby regulating their expression levels and activities [ 44 ]. Lv et al revealed that miR-135b-5p is a target of MALAT1, and MALAT1 regulates the cell viability by regulating miR-135b-5p expression in Parkinson’s disease [ 45 ]. Jia et al showed that MALAT1 is involved in ischemia-reperfusion injury via miR-195a-5p [ 46 ].…”

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

“…HOTAIR may also promote apoptosis of neuronal cells through microRNA-126-5p (miR-126-5p)/RAB3A-interacting protein (RAB3IP) axis (Lin et al, 2019 ). Furthermore, MALAT1 contributed to the apoptosis of DAs by combining with miR-124 and microRNA-135-5p (miR-135-5p; Liu W. et al, 2017 ; Lv et al, 2021 ).…”

Long Intergenic Noncoding RNAs Affect Biological Pathways Underlying Autoimmune and Neurodegenerative Disorders

“…MALAT1 expression is also upregulated in PD brains as well as in mouse and cellular models of PD [75,[130][131][132][133][134] and was suggested to promote neuronal apoptosis by acting as a miR-124 sponge [132]. Many studies have reported significant downregulation of miR-124 in PD models, which prevents it from playing its neuroprotective role against dopaminergic cell death, autophagy dysregulation, neuroinflammation, and oxidative damage (Table S1) [135].…”

“…Many studies have reported significant downregulation of miR-124 in PD models, which prevents it from playing its neuroprotective role against dopaminergic cell death, autophagy dysregulation, neuroinflammation, and oxidative damage (Table S1 ) [ 135 ]. Furthermore, MALAT1 can contribute to MPP + -induced apoptosis by regulating the miR-205-5p/LRRK2, miR-135b-5p/GPNMB (glycoprotein nonmetastatic melanoma protein B), and miR‐124‐3p/DAPK1 axes (Table S1 ) [ 130 , 131 , 133 ]. Mutations in the LRRK2 kinase gene, described as a frequent cause of both familial and sporadic PD, result in mitochondrial dysfunction, whereas DAPK1 is involved in dopaminergic neuron degeneration in PD [ 130 , 131 , 133 ].…”

“…Furthermore, MALAT1 can contribute to MPP + -induced apoptosis by regulating the miR-205-5p/LRRK2, miR-135b-5p/GPNMB (glycoprotein nonmetastatic melanoma protein B), and miR‐124‐3p/DAPK1 axes (Table S1 ) [ 130 , 131 , 133 ]. Mutations in the LRRK2 kinase gene, described as a frequent cause of both familial and sporadic PD, result in mitochondrial dysfunction, whereas DAPK1 is involved in dopaminergic neuron degeneration in PD [ 130 , 131 , 133 ]. A recent study revealed that MALAT1 can also induce inflammasome activation and reactive oxygen species production in PD models through epigenetic suppression of NRF2 (NF-E2-related factor 2) expression [ 134 ].…”