Functional roles and networks of non-coding RNAs in the pathogenesis of neurodegenerative diseases

Wu, Yi-Ying; Kuo, Hung-Chih

doi:10.1186/s12929-020-00636-z

Journal of Biomedical Science

Table 2 ncRNAs and related processes in Parkinson’s disease

From: Functional roles and networks of non-coding RNAs in the pathogenesis of neurodegenerative diseases

	Name	up/down regulation	Stimulation	Description	Model	Ref
lncRNAs	HOTAIR	up	MPTP	correlated with LRRK2 upregulation and activating caspase 3 dependent apoptosis	mouse model	[58]
	HOTAIR	up	MPTP	blocking miR-126-5p/RAB3IP interaction and promoting DA neurona death	mouse model	[59]
	NEAT1	up	MPTP	Positively correlated with treated MPTP concentration. NEAT1 upregulation promotes Bax/BCl ratio, caspase 3 activity and α-synuclein expression. NEAT1 knokdown promotes cell viability and supresses apotosis.	mice, cell line	[60]
	NEAT1	up	MPTP	NEAT1 correlated with neuroinflammation after MPP+ treatment (IL-1b, IL-6 and TNF-a upregulation). NEAT1 serves as miR-124 decoy and promotes cell death and apoptosis.	mice, cell line	[61]
	NEAT1	up	MPTP	NEAT1 promotes PINK1 protein stability via preventing degredation. NEAT1 positively correlated to LC3-II/LC3-I level and promotes autophogy.	mice, cell line	[62]
	NORAD	down	MPP+	NORAD protects cell against MPP+ induced cytotixity inclduing caspase3/7, ROS and LDH activity with unknown mechanism.	cell line	[12]
	p21	up	MPTP	p21 positvely regulates TRPM2 expression by targeting miR-625. p21 serves as a miR-625 decoy and inhibits TRPM2 function in causing neuronal injury.	cell line	[63]
	p21	up	MPTP	p21 is miR-1277-5p decoy and prevents miR-1277-5p directly targeting a-synuclein expression. P21/miR-1277-5p/a-synuclein axis leads to apoptosis in MPP+ induced PD models.	mouse	[64]
	SNHG1	up	MPTP	SNHG-1 is a miRNA sponge of miR-221/222 and prevents p27 targeting and activation of mTOR pathway. Downregulation of SNHG1 attenuated MPP+ induced decreases in LC3-II (an autophagic marker) levels and cytotoxicity through the miR-221/222/p27/mTOR pathway.	cell line	[65]
	SNHG1	down		miR-15 decoy and inhibit miR-15 function	cell line	[66]
	SNHG1	up	LPS	Upregulation of SNHG1 promotes neuroinflammation in BV2 microglia of PD models. SNHG-1 functioned as a competing endogenous RNA for miR-7 to regulate NLRP3 expression leading to the activation of NLRP3 inflammasome.	mice, cell line	[67]
	U1 splicesomeal lncRNA, RP11-462G22.1	up		Upregulated in patiensts’ leukocyte, amygdala and substantia-nigra. Computational prediction shows miRNA decoy, and exhibit a more complex secondary stem-loop structure. Potentially as decoy of 21 different miRNAs (potential ceRNA).	PD patient tissue	[68]
	tRNA-derived fragment			A list of tRNA-derived fragment are consistently founded in pateits’ CSF, serum and cortex. The tRNA-derived fragment are the biomarkers of PD.	PD CSF, cortex, serum	[69]
NATs	UCHL1-AS		MPTP	UCHL1-AS is an antisense to the mouse ubiquitin carboxy terminal hydrolase L1 and activates transcription of UCHL1. UCHL1 is under the regulation of Nurr1(a major transcription factor) in dopaminergic differentiation, maintenance and related to cellular stress in the brain.	mouse, PD patient	[25]
NATs	GDNF-AS		6-OHDA	GDNF-AS is coded for GDNF and enable to promote GDNF expression by 2 fold. GDNF-AS delivery by Adeno-associated virus was able to ameliorate motor deficits and neurodegeneration of DA neurons in a PD mouse models lesioned by6-OHDA treatment.	mouse	[70]
circRNAs	circSNCA	up	MMP+	circSNCA serve as a miR-7 sponge and prevents miR-7 targeting SNCA expression. Increased SNCA induce pro-apoptotic genes (CASP3, BAX, PTEN and P53). Knockdown of circSNCA shows the anti-apoptotic gene (BCL2) expression and prevents apoptosis.	cell line	[12]
miRNAs	miR-126	up	6-OHDA	miR-126 directly targets p85b, IRS-1, SPRED1 and impaires IGF-1/PI3K/AKT signaling. miR-126 leads to 6-OHDA induced neurotoxity.	cell line	[71]
	miR-126-5p	down		miR-126-5p increase cell proliferation and reduce apotosis via targeting RAB3IP	cell line	[59]
	miR-133a/b			miR-133 targeted PITX3 mutations/polymorphisms are not related to PD risk.	human genome sequence	[72]
	miR-133b	down		miR-133b targets RhoA (inhibitor of axonal growth) and indcue axonal outgrowth. miR-133b inhibits a-synuclein expression, Bcl/bax ratio and activates pAkt for neuronal survival.	cell line	[72]
	miR-153	down	MPP+	miR-153 reduces p38 activation and prevents neuro-inflammation induced apoptosis	mouse primary cortical neuron	[73]
	miR-16-1	up		miR-16-1 targets Hsp70 3’UTR and negatively regulate a-synuclein aggregation	SH-SY5Y	[74]
	miR-183	up		miR-183 promotes apotosis of substantia nigra neuron by inhibit the expression of OSMR.	cell line	[75]
	miR-205	down		mir-205 suppresses the expression of LRRK2 protein through a conserved-binding site at the 3′-UTR of LRRK2 gene and promotes neurite outgrowth.	PD brain section	[76]
	miR-22	down	6-OHDA	miR-22 overexpression downregulates the level of TRPM7, exhibited neuroprotective and reversal effect on the 6-OHDA-induced PCL2 cell growth and apotosis.	cell line	[77]
	miR-221	down	MPP+	DJ-1 may increase miR-221 expression through the MAPK/ERK pathway, leading the repression of apototic molecules BIM.	cell line	[70]
	miR-27a/b	down	CCCP	miR-27a/b suppress PINK1 expression through targeting 3′ UTR. Donwregulated PINK1 by miR-27a/b prevents its aggregation upon mitochondria damage and inhibits lysosomal degradation of damaged mitochondria.	cell line	[21]
	miR-342-3p	up	MPTP	miR-342-3p directly targets PAK1(p21-activated kinase 1) in Wnt signallg pathway. miR-342-3p also reduce expression of GLT-1, GLAST, and leads to reduce TH expression and the related apoptosis.	mouse	[6]
	miR-34b/c	down		miR-34b/c targets α-synuclein 3’UTR and reduces expression. In SNP of α-synuclein in Parkinson’s disease, failed miR-34b/c targeting causes α-synuclein expression and the related PD pathogenesis.	cell line	[78]
	miR-494	up	MPTP	miR-494 directly binds to 3′-UTR of DJ-1 transcript and inversely regulates the expression of DJ-1 which compromise anti-oxidative defence of cell.	mice	[79]
	miR-7	down		miR-7 represses a-synuclein protein level through binding 3′ UTR of A4 component of amyloid precursor (SCNA; gene name of a-synuclein) and protects cell against oxidative stress.	PD brain section	[12]
	miR-7/miR-153	down	MPP+	Both miR-7 and miR-153 activate p70S6K/pS6RP/SAPK/JNK mediated mTOR pathway.	mouse primary cortical neuron	[73]
	miR-96	up	MPTP	CACNG5 is the target gene of miR-96. CACNG5 and BCL2 inhibition are linked to the activation of iNOS and apotosis.	mice	[80]

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ISSN: 1423-0127

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