MicroRNA-326 Inhibits Apoptosis and Promotes Proliferation of Dopaminergic Neurons in Parkinson’s Disease Through Suppression of KLK7-Mediated MAPK Signaling Pathway

Zhang, Yizhi; Xu, Weiwei; Nan, Shanji; Chang, Meiji; Jia, Fan

doi:10.1007/s12031-019-01349-1

Cited by 27 publications

(16 citation statements)

References 51 publications

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“…As a matter of fact, high miR-326 is proved to correlate with long overall survival of patients with glioblastoma, the common type of brain tumor [24]. Also, miR-326 expression has been further evidenced to reduce in Parkinson's disease and miR-326 could suppress apoptosis of dopaminergic neurons and reduce inflammatory response [25]. Except for that, the reduction in miR-326-5p is manifested in endothelial progenitor cells in the course of myocardial infarction, and introduction of endothelial progenitor cells overexpressing could promote cardiac function recovery [11].…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Restored microRNA-326-5p Inhibits Neuronal Apoptosis and Attenuates Mitochondrial Damage via Suppressing STAT3 in Cerebral Ischemia/Reperfusion Injury

et al. 2021

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Studies have greatly explored the role of microRNAs (miRNAs) in cerebral ischemia/reperfusion injury (CI/RI). But the specific mechanism of miR-326-5p in CI/RI is still elusive. Hence, this study was to unmask the mechanism of miR-326-5p/signal transducer and activator of transcription-3 (STAT3) axis in CI/RI. Two models (oxygen and glucose deprivation [OGD] in primary rat cortical neurons and middle cerebral artery occlusion [MCAO] in Sprague–Dawley rats) were established to mimic CI/RI in vitro and in vivo, respectively. Loss- and gain-of function assays were performed with OGD-treated neurons and with MCAO rats. Afterward, viability, apoptosis, oxidative stress and mitochondrial membrane potential in OGD-treated neurons were tested, as well as pathological changes, apoptosis and mitochondrial membrane potential in brain tissues of MCAO rats. Mitofusin-2 (Mfn2), miR-326-5p and STAT3 expression in OGD-treated neurons and in brain tissues of MCAO rats were detected. Mfn2 and miR-326-5p were reduced, and STAT3 was elevated in OGD-treated neurons and brain tissues of MCAO rats. miR-326-5p targeted and negatively regulated STAT3 expression. Restoring miR-326-5p or reducing STAT3 reinforced viability, inhibited apoptosis and oxidative stress, increased mitochondrial membrane potential and increased Mfn2 expression in OGD-treated neurons. Up-regulating miR-326-5p or down-regulating STAT3 relieved pathological changes, inhibited apoptosis and elevated mitochondrial membrane potential and Mfn2 expression in brain tissues of rats with MCAO. This study elucidates that up-regulated miR-326-5p or down-regulated STAT3 protects against CI/RI by elevating Mfn2 expression.

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Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Restored microRNA-326-5p Inhibits Neuronal Apoptosis and Attenuates Mitochondrial Damage via Suppressing STAT3 in Cerebral Ischemia/Reperfusion Injury

et al. 2021

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“…The expression of miR-326 was shown to be down-regulated in MPTP-induced PD mice (Zhao et al, 2019). MiR-326 over-expression ameliorates the motor dysfunction and the structural abnormality of the SNpc (increase content of DA, SOD, GSH-Px, and TH positive expression) in PD mice (Zhang et al, 2019). In addition, miR-326 overexpression also inhibits numerous immunomodulatory factors such as TNF-α, IL-1, IL-6, and INF-γ.…”

Section: Mir-326mentioning

confidence: 95%

MicroRNA Dysregulation in Parkinson’s Disease: A Narrative Review

et al. 2021

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Parkinson’s disease (PD) is a severely debilitating neurodegenerative disease, affecting the motor system, leading to resting tremor, cogwheel rigidity, bradykinesia, walking and gait difficulties, and postural instability. The severe loss of dopaminergic neurons in the substantia nigra pars compacta causes striatal dopamine deficiency and the presence of Lewy bodies indicates a pathological hallmark of PD. Although the current treatment of PD aims to preserve dopaminergic neurons or to replace dopamine depletion in the brain, it is notable that complete recovery from the disease is yet to be achieved. Given the complexity and multisystem effects of PD, the underlying mechanisms of PD pathogenesis are yet to be elucidated. The advancement of medical technologies has given some insights in understanding the mechanism and potential treatment of PD with a special interest in the role of microRNAs (miRNAs) to unravel the pathophysiology of PD. In PD patients, it was found that striatal brain tissue and dopaminergic neurons from the substantia nigra demonstrated dysregulated miRNAs expression profiles. Hence, dysregulation of miRNAs may contribute to the pathogenesis of PD through modulation of PD-associated gene and protein expression. This review will discuss recent findings on PD-associated miRNAs dysregulation, from the regulation of PD-associated genes, dopaminergic neuron survival, α-synuclein-induced inflammation and circulating miRNAs. The next section of this review also provides an update on the potential uses of miRNAs as diagnostic biomarkers and therapeutic tools for PD.

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“…37 This evidence indicates that miR-212-5p plays a regulatory role and exhibits neuroprotective effects in PD. In addition, miR-324-3p is down-regulated in PD patients, 38 while miR-326 promotes autophagy in dopaminergic neurons in PD mice, 39 inhibits apoptosis and promotes proliferation of dopaminergic neurons in PD, 40 which demonstrates that miR-324-3p and miR-326 are ideal new targets for PD treatment in the future. Moreover, recent studies by He et al 41 have demonstrated that miR-326 improved cognitive function and inhibited neuronal apoptosis in mice with Alzheimer's disease (AD) through a related signaling pathway.…”

Section: Figurementioning

confidence: 95%

<p>Functional Analysis of the 3ʹ Untranslated Region of the Human <em>GRIN1</em> Gene in Regulating Gene Expression in vitro</p>

Liu

Jinghua

et al. 2020

NDT

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Purpose: Abnormal expression of the NR1 subunit of the N-methyl-d-aspartate (NMDA) receptor may potentially increase the susceptibility to neuropsychiatric diseases. The purpose of this study was to investigate the functional sequence of the 3ʹUTR of the human GRIN1 gene, which encodes the GluN1 receptor to determine the effect on the expression of GluN1 receptor. Methods: We transferred seven recombinant pmirGLO recombinant vectors containing the 3ʹUTR truncated fragment of the GRIN1 gene into HEK-293, SK-N-SH, and U87 cell lines and compared the relative fluorescence intensity of adjacent length fragments. The TargetScan database was used to predict miRNAs. Then, miRNA mimics/inhibitors were co-transfected into the three cell lines with the 3ʹUTR of GRIN1 (pmirGLO-GRIN1), to investigate their influence on GRIN1 gene expression. Results: Compared with the pmirGLo-Basic vector, the relative fluorescence intensity of the complete GRIN1 gene 3ʹUTR recombinant sequence −27 bp-+1284 bp (the next base of the stop codon is +1) was significantly decreased in all three cell lines. The relative fluorescence intensities were significantly different between −27 bp-+294 bp and −27 bp-+497 bp regions, and between −27 bp-+708 bp and −27 bp-+907 bp regions. According to the prediction of the TargetScan database and analysis, miR-212-5p, miR-324-3p and miR-326 may bind to +295 bp-+497 bp, while miR-491-5p may bind to +798 bp-+907 bp. After co-transfection of miRNA mimic/inhibitor or mimic/inhibitor NC with a recombinant vector in the 3ʹUTR region of GRIN1 gene, we found that has-miR-491-5p inhibited GRIN1 expression significantly in all three cell lines, while has-miR-326 inhibitor upregulated GRIN1 expression in HEK-293 and U87 cells. Conclusion: miR-491-5p may bind to the 3ʹUTR of the GRIN1 gene (+799 bp-+805 bp, the next base of the stop codon is +1) and down-regulate gene expression in HEK-293, SK-N-SH, and U87 cell lines, which implicates a potential role of miR-491-5p in central nervous system diseases.

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MicroRNA-326 Inhibits Apoptosis and Promotes Proliferation of Dopaminergic Neurons in Parkinson’s Disease Through Suppression of KLK7-Mediated MAPK Signaling Pathway

Cited by 27 publications

References 51 publications

RETRACTED ARTICLE: Restored microRNA-326-5p Inhibits Neuronal Apoptosis and Attenuates Mitochondrial Damage via Suppressing STAT3 in Cerebral Ischemia/Reperfusion Injury

RETRACTED ARTICLE: Restored microRNA-326-5p Inhibits Neuronal Apoptosis and Attenuates Mitochondrial Damage via Suppressing STAT3 in Cerebral Ischemia/Reperfusion Injury

MicroRNA Dysregulation in Parkinson’s Disease: A Narrative Review

<p>Functional Analysis of the 3ʹ Untranslated Region of the Human <em>GRIN1</em> Gene in Regulating Gene Expression in vitro</p>

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