Table 1 ncRNAs and related processes in Huntington’s disease

lncRNA

HAR1F, HAR1R

down

HAR1F and HAR1R are direct targets of REST. Leading to thr repression of several important neuronal genes.

human HD brain_striatum

[23]

DGCR5

down

DGCR5 is a REST target lncRNA, which plays an important transcriptional regulatory role in HD

human HD brain

[24]

MEG3

down

MEG3 is a direct target of REST and found in the chromatin compartment of the cell in association with PRC2 complex

human HD brain

[25, 26]

MEG3, NEAT1

up

Loss of function of Meg3 and Neat1 modulated mHtt aggregates and downregulation of the Tp53 expression

R6/2 mouse cortex

[27]

NEAT1-L, NEAT1-S

up

NEAT1 provides neuroprotection against mHtt-induced cytotoxicity (NEAT1-L) and oxidative stress-induced injury (NEAT1-S).

R6/2 mouse brain

[27-29]

TUG1

up

TUG1 is a direct downstream target of p53 and could modulate mHTT-induced cytotoxicity by p53 activation. TUG1 could be able to binding to the PRC2 epigenetic regulatory complex.

human HD brain

[30]

TUNA

down

TUNA expression was associated with pathological disease severity, decreasing significantly as the disease grade increased.

human HD brain_caudate nucleus

[31]

LINC00341

up

unknown

human HD brain

[25]

RPS20P22

up

RPS20P22 regulates RPS20, which decreases will lead to accumulation of p53.

human HD brain

[25]

LINC00342

down

unknown

human HD brain

[25]

NATs

Abhd11-os

down

Abhd11-os (called Abhd11-AS1 in human) attenuate the mHtt-induced tocixity and contribute to striatal vulnerability in HD.

R6/2 mouse model

[32]

HTTAS_v1

down

HttAS-v1 reduces endogenous mHtt tanscript level through RISC-dependent miR-like mechanism

human HD brain_frontal cortex

[7]

BDNF-AS

BDNF-AS was associated with the recruitment of polycomb repressive complex 2 (PRC2), which locally induces the trimethylation of histone H3K27 within the locus and in that way plays an important role in the development of HD.

[25, 33, 34]

others

sCAGs

up

sCAG significantly decreased HTT-mediated neuronal viability in an Ago2-dependent mechanism.

R6/2 mouse striatum; human HD brain

[35]

miRNAs

miR-9*

down

miR-9* targets the components of the REST repressor complex, CoREST and modulating the neurotrophic genes expression.

HD patient

[26]

miR-10b-5p

up

miR-10b-5p targets BDNF and correlated to aberrant polycomb repressive complex2 (PRC2) regulation.

HD brain_profrontal cortices

[36]

miR-22

down

miR-22 was found to target HDAC4, Rcor1 (CoREST) and Rgs2 mRNA and achieve neuroprotection and inhibit neurodegeneration.

HD brain

[26]

miR-27a

down

miR-27a increases MDR-1 expression; miR-27a can decrease the mHtt aggregates possibly through MDR-1 modulation.

R6/2 mice

[37]

miR-34a-5p

down

miR-34a downregulated SIRT1 through binding the 3′ UTR of sirt1 mRNA.

R6/2 mice

[38]

miR-34b

up

miR-34b is a P53-regulated miRNA and the levels may influence mHTT cytoplasmic distribution and toxicity

HD patient, plasma

[39]

miR-214, miR-125b, miR-146a, miR-150

down

miR-214, miR-150, miR-146a and miR-125b target both huamn HTT and mouse Htt.

STHdh(Q111)/Hdh(Q111) cells

[40]

miR-125b, miR-146a, miR-150

down

miR-146a, miR-150 and miR-125b are decreased in striatum of R6/2 mice. miR-125b and miR-150 target p53, which in turn regulates RelA/NFkB and miR-146a expressions

STHdhQ111/HdhQ111 cells

[41]

miR-124

down

Decreased miR-124 expression could increase CCNA2 and is involved in deregulation of cell cycle

STHdhQ111/HdhQ111 cells

[42]

miR-124a

down

The neuronal-specific miR-124 is dysregulated in HD tissues, probably as a result of increased repression by REST.

R6/2 mouse brain

[43]

miR-128a

down

miR-128a targets the 3′ UTR of HTT, Huntingtin Interaction Protein 1 (HIP1) and SP1.

Transgenic HD monkeys

[44]

miR132

down

The level of miR-132 associated with Ago2. miR-132 supplementation produced symptomatic improvement of motor function and lifespan.

R6/2 mice

[45]

miR-212/miR-132

down

miR-212/miR-132 clusters are significantly associated with CAG length and implicated in neuronal survival and shows strongest down-regulation in the striatum.

HD transgenic mice

[35]

miR-196a

up

miR-196a might improve mitochondrial function by the upregulation of CBP and PGC-1α to promote oxidation phosphorylation and reduce oxidative stress, which was consistent with the amelioration of cytotoxicity by miR-196a.

HD brain, striatum

[46]

miR-196a

up

The higher expression of RAN binding protein 10 (RANBP10) in the brains of HD transgenic mice and exacerbates neuronal morphology and intracellular transport. miR-196a suppress the expression of RANBP10 through binding to its 3’UTR.

HD transgenic mice brain

[47]

miR-196a

up

miR-196a decreased mHTT expression and pathological aggregates through alteration of several neuronal regulatory pathways including ubiquitin-proteasome systems, gliosis and cAMP response element-binding protein pathway.

HD-iPSC derived neurons

[48]

miR-19, miR-146a, miR-432

down

The increase in the expressions of PCNA, CHEK1 and CCNA2 was found to be the result of decreased expressions of miR-432, miR-146a, and (miR-19a and miR-146a) respectively. Exogenous expressions of these miR-432 and miR-146a in HD cells rescued the abnormalities in cell cycle and apoptosis.

STHdh(Q111)/Hdh(Q111) cells

[43]