The Long Non-Coding RNA NR3C2-8:1 Promotes p53-Mediated Apoptosis through the miR-129-5p/USP10 Axis in Amyotrophic Lateral Sclerosis

Abstract

Motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is a form of apoptosis, but the mechanisms underlying this neuronal cell death remain unclear. Numerous studies demonstrate abnormally elevated and active p53 in the central nervous system of ALS patients. Activation of p53-regulated pro-apoptotic signaling pathways may trigger motor neuron death. We previously reported decreased expression of the long non-coding RNA NR3C2-8:1 (Lnc-NR3C) in leukocytes of ALS patients. Here, we show lnc-NR3C promotes p53-mediated cell death in ALS by upregulating USP10 and promoting lnc-NR3C-triggered p53 activation, resulting in cell death. Conversely, lnc-NR3C knockdown inhibited USP10-triggered p53 activation, thereby protecting cells against oxidative stress. As a competitive endogenous RNA, lnc-NR3C competitively binds miR-129-5p, regulating the usp10/p53 axis. Elucidating the link between Lnc-NR3C and the USP10/p53 axis in an ALS cell model reveals a role for long non-coding RNAs in activating apoptosis. This provides new therapeutic opportunities in ALS.

Identification of key genes and signaling pathway in the pathogenesis of Huntington's disease via bioinformatics and next generation sequencing data analysis

“…Recent studies have shown that SERPINA1 [563], LRRK2 [522], CHRNA4 [564], CD22 [565], TF (transferrin) ssociated tyrosine kinase) [579], FGF14 [580], INSC (INSC spindle orientation adaptor protein) [581], BARHL1 [582], PRKCH (protein kinase C eta) [583], SLC24A4 [584], TMEM176B [585], MBP (myelin basic protein) [586], ACAN (aggrecan) [587], SHH (sonic hedgehog signaling molecule) [588], SIRT2 [589], RBP4 [590], ISM1 [591], HOXB6 [592], CDH13 [593], NTF3 [594], TRPC6 [595], MMP3 [596], HLA-DRB5 [597], HLA-DRB1 [546], CD74 [598], VWF (von Willebrand factor) [599], MDGA1 [600], ANGPT2 [601], NEDD4L [602], CASP1 [603], CHRNA5 [604], CCND2 [605], BRCA2 [606], TET1 [607], ZBTB20 [608], OAS1 [609], EGFR (epidermal growth factor receptor) [610], ABCA1 [611], PLXNA4 [612], FOXG1 [613], WEE1 [433], MAP1B [614], ANK1 [615], GRM3 [436], COMT (catechol-O-methyltransferase) [616], SLC10A4 [617], GPR39 [618] and LIFR (LIF receptor subunit alpha) [562] could promote Alzheimer’s disease progression. SERPINA1 [619], LRRK2 [620], CHRNA4 [621], TLR2 [622], MOBP (myelin associated oligodendrocyte basic protein) [623], AATK (apoptosis associated tyrosine kinase) [624], MBP (myelin basic protein) [625], SHH (sonic hedgehog signaling molecule) [626], XDH (xanthine dehydrogenase) [627], RBP4 [628], GRIA2 [629], NR3C2 [630], HLA-DRB5 [631], HLA-DRA [631], NEDD4L [632], CASP1 [633], EFNB2 [634], CYP7B1 [635], EGFR (epidermal growth factor receptor) [636], MAP1B [637], GRM3 [638<...…”