MicroRNA-5572 Is a Novel MicroRNA-Regulating SLC30A3 in Sporadic Amyotrophic Lateral Sclerosis

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive degenerative disease caused by the loss of motor neurons. Although the pathogenesis of sporadic ALS (sALS) remains unclear, it has recently been suggested that disorders of microRNA (miRNA) may be involved in neurodegenerative conditions. The purpose of this study was to investigate miRNA levels in sALS and the target genes of miRNA. Microarray and real-time RT-PCR analyses revealed significantly-decreased levels of miR-139-5p and significantly increased levels of miR-5572 in the spinal cords of sALS patients compared with those in controls. We then focused on miR-5572, which has not been reported in ALS, and determined its target gene. By using TargetScan, we predicted SLC30A3 as the candidate target gene of miR-5572. In a previous study, we found decreased SLC30A3 levels in the spinal cords of sALS patients. We revealed that SLC30A3 was regulated by miR-5572. Taken together, these results demonstrate that the level of novel miRNA miR-5572 is increased in sALS and that SLC30A3 is one of the target genes regulated by miR-5572.

Upregulation of β-catenin due to loss of miR-139 contributes to motor neuron death in amyotrophic lateral sclerosis

“…miRNAs are post-transcriptional regulators of gene expression that suppress the translation of their target mRNAs and can fine-tune signaling pathways ( Ha and Kim, 2014 ). Dysregulation of miRNA expression has been observed in fALS and sALS ( Emde et al., 2015 ; Figueroa-Romero et al., 2016 ; De Santis et al., 2017 ; Reichenstein et al., 2019 ; Tung et al., 2019 ; Kurita et al., 2020 ). Hence, we used small RNA sequencing (RNA-seq) to profile miRNA expression levels in our disease model.…”

“…MiR-139-5p, hereafter referred to as miR-139, was the only miRNA that was commonly downregulated across fALS and sALS datasets. Furthermore, miR-139 is downregulated in patient serum and postmortem spinal cord tissue ( Raheja et al., 2018 ; Kurita et al., 2020 ). qRT-PCR analysis of our iPSC-derived MNs confirmed the downregulation of miR-139 in FUS H517Q/H517Q and H517Q/+ MNs compared to healthy controls ( Figure 2 D), validating our sequencing results.…”

Bioinformatics and next generation sequencing data analysis to identify key genes and pathways influencing in Parkinson’s disease

“…WNT1 [182], NRGN (neurogranin) [183], CCK (cholecystokinin) [184], RGS4 [185], PLK2 [186], LINGO1 [187], UNC5D [188], MEF2D [189], CX3CL1 [190], PIN1 [191], RET (ret proto-oncogene) [192], NME1 [193], STX1B [194], CDK5 [195], NPTX2 [196], VAMP2 [197], PRKAR1B [198], CAP2 [150], SNCB (synuclein beta) [199], AP2M1 [200], S100A9 [201], TLR8 [202], SERPINA1 [203], CCR5 [204], NOD2 [205], TLR7 [202], HGF (hepatocyte growth factor) [206], TLR2 [207], PTPRC (protein tyrosine phosphatase receptor type C) [208], C3 [209], LAMP3 [210], GLI1 [211], GPR4 [212], TLR1 [213], OSMR (oncostatin M receptor) [214], NFATC2 [215], GPNMB (glycoprotein nmb) [216], NQO1 [217], B2M [218], TRDN (triadin) [219], HK2 [220], NEDD4 [221], ATP6 [222], COX2 [223], CASP6 [224], MYD88 [225], NFKBIA (NFKB inhibitor alpha) [226], IL13RA1 [227], ND1 [228], TP53INP1 [229], CSF1 [230], ITPKB (inositol-trisphosphate 3-kinase B) [231], ANXA1 [232], SUMO4 [233], ITGA8 [234] and REST (RE1 silencing transcription factor) [235] have been shown to be activated in PD . WNT1 [236], RTN4R [237], MEF2D [238], CX3CL1 [239], PIN1 [240], UNC13A [241], CDK5 [242], SLC30A3 [243], TUBA4A [244], BCL2A1 [245], CHI3L1 [246], SERPINA1 [247], CCR5 [248], C7 [249], S100A4 [250], C1QB [251], SPP1 [252], TLR7 [253], TLR2 [...…”

Bioinformatics analyses of significant genes, related pathways and candidate prognostic biomarkers in Alzheimer’s disease

“…FLT3 [162], CHRNB4 [163], PAK1 [164], CHRNB3 [165], GRIN2A [166], CHRNA6 [167], PENK (proenkephalin) [168], CHRNB4 [169], IGF2 [170], TLR9 [171] and CACNG5 [172] were revealed to serve an important role in Parkinson’s disease, but these genes might be novel target for AD. The expression of SLC30A3 [173], NEFH (neurofilament heavy) [174], SYNGR4 [175], S100A4 [176], HSPB1 [177] and KIF5A [178] are associated with amyotrophic lateral sclerosis, but these genes might be novel target for AD.…”