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Metabolic Brain Disease

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17.01.2023 | Original Article

LncRNA CRNDE binds hnRNPA1 to facilitate carbon monoxide poisoning-induced delayed encephalopathy via inhibiting UCHL5-mediated SMO deubiquitination

verfasst von: Zuolong Liu, Miao Bian, Li Pang

Erschienen in: Metabolic Brain Disease | Ausgabe 3/2023

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Abstract

Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is one of the most common complications following carbon monoxide intoxication. Long noncoding RNAs (lncRNAs) exert critical functions in numerous neurological disorders. We intended to investigate the role of CRNDE in DEACMP. The DEACMP model in rats and the oxygen–glucose deprivation/reoxygenation (OGD/R) model in PC-12 cells were established. Brain and cell injuries were assessed with H&E staining, Nissl staining, TUNEL and CCK8 assays, respectively. Related proteins and RNAs were quantified with western blot and qRT-PCR. The N6-methyladenosine (m6A) level was determined using MeRIP-qPCR and immunofluorescence. Loss and gain function studies were performed to investigate the biological function of CRNDE. The potential mechanisms between each factor were explored using RNA immunoprecipitation, RNA-pull down and co-immunoprecipitation. CRNDE was increased in the hippocampal tissues of DEACMP rats and in OGD/R-treated PC-12 cells, which was positively correlated to m6A modification. Knockdown of CRNDE reduced cell damage and elevated UCHL5 and SMO expressions in OGD/R-treated PC-12 cells. hnRNPA1 was upregulated in DEACMP. In addition, inhibiting hnRNPA1 prevented apoptosis in PC-12 cells subjected to OGD/R. hnRNPA1 bound to CRNDE and remained in the nucleus, which inhibited UCHL5 expression through the formation of CRNDE-hnRNPA1-mRNA complex. UCHL5 could inhibit SMO ubiquitination and suppress PC-12 cell apoptosis during OGD/R. CRNDE silencing blocked brain injury in DEACMP, while knocking down UCHL5 reversed these effects. CRNDE interacted with hnRNPA1 to facilitate DEACMP via inhibition of UCHL5-mediated SMO deubiquitination. CRNDE might be a latent therapeutic target for treating DEACMP.

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Chechneva OV, Mayrhofer F, Daugherty DJ, Krishnamurty RG, Bannerman P, Pleasure DE, Deng W (2014) A Smoothened receptor agonist is neuroprotective and promotes regeneration after ischemic brain injury. Cell Death Dis 5:e1481PubMedPubMedCentralCrossRef

Chen Y, Zhou J (2017) LncRNAs: macromolecules with big roles in neurobiology and neurological diseases. Metab Brain Dis 32:281–291PubMedCrossRef

Chokkalla AK, Mehta SL, Kim T, Chelluboina B, Kim J, Vemuganti R (2019) Transient focal ischemia significantly alters the m(6)A epitranscriptomic tagging of RNAs in the brain. Stroke 50:2912–2921PubMedPubMedCentralCrossRef

Ellis BC, Molloy PL, Graham LD (2012) CRNDE: A long non-coding RNA involved in cancer, neurobiology, and development. Front Genet 3:270PubMedPubMedCentralCrossRef

Ferre F, Colantoni A, Helmer-Citterich M (2016) Revealing protein-lncRNA interaction. Brief Bioinform 17:106–116PubMedCrossRef

Fu CH, Lai FF, Chen S, Yan CX, Zhang BH, Fang CZ, Wang GH (2020a) Silencing of long non-coding RNA CRNDE promotes autophagy and alleviates neonatal hypoxic-ischemic brain damage in rats. Mol Cell Biochem 472:1–8PubMedCrossRef

Fu CH, Zhang BH, Fang CZ, Yan CX, Lai FF, Chen S, Wang GH (2020b) Long non-coding RNA CRNDE deteriorates intrauterine infection-induced neonatal brain injury. Mol Cell Probes 52:101565PubMedCrossRef

Fukui S, Nagasaka K, Miyagawa Y, Kikuchi-Koike R, Kawata Y, Kanda R, Ichinose T, Sugihara T, Hiraike H, Wada-Hiraike O, Sasajima Y, Ayabe T (2019) The proteasome deubiquitinase inhibitor bAP15 downregulates TGF-beta/Smad signaling and induces apoptosis via UCHL5 inhibition in ovarian cancer. Oncotarget 10:5932–5948PubMedPubMedCentralCrossRef

Geraldo AF, Silva C, Neutel D, Neto LL, Albuquerque L (2014) Delayed leukoencephalopathy after acute carbon monoxide intoxication. J Radiol Case Rep 8:1–8PubMedPubMedCentral

Huang YQ, Peng ZR, Huang FL, Yang AL (2020) Mechanism of delayed encephalopathy after acute carbon monoxide poisoning. Neural Regen Res 15:2286–2295PubMedPubMedCentralCrossRef

Huisman B, Manske G, Carney S, Kalantry S (2017) Functional dissection of the m6A RNA modification. Trends Biochem Sci 42:85–86PubMedPubMedCentralCrossRef

Kahl A, Blanco I, Jackman K, Baskar J, Milaganur Mohan H, Rodney-Sandy R, Zhang S, Iadecola C, Hochrainer K (2018) Cerebral ischemia induces the aggregation of proteins linked to neurodegenerative diseases. Sci Rep 8:2701PubMedPubMedCentralCrossRef

Kikuchi M, Ogishima S, Miyamoto T, Miyashita A, Kuwano R, Nakaya J, Tanaka H (2013) Identification of unstable network modules reveals disease modules associated with the progression of Alzheimer’s disease. PLoS ONE 8:e76162PubMedPubMedCentralCrossRef

Lan X, Yan J, Ren J, Zhong B, Li J, Li Y, Liu L, Yi J, Sun Q, Yang X, Sun J, Meng L, Zhu W, Holmdahl R, Li D, Lu S (2016) A novel long noncoding RNA Lnc-HC binds hnRNPA2B1 to regulate expressions of Cyp7a1 and Abca1 in hepatocytic cholesterol metabolism. Hepatology 64:58–72PubMedCrossRef

Levin MC, Lee S, Gardner LA, Shin Y, Douglas JN, Salapa H (2017) Autoantibodies to heterogeneous nuclear ribonuclear protein A1 (hnRNPA1) cause altered “ribostasis” and neurodegeneration; the legacy of HAM/TSP as a model of progressive multiple sclerosis. J Neuroimmunol 304:56–62PubMedCrossRef

Li Q, Bi MJ, Bi WK, Kang H, le Yan J, Guo YL (2016) Edaravone attenuates brain damage in rats after acute CO poisoning through inhibiting apoptosis and oxidative stress. Environ Toxicol 31:372–379PubMedCrossRef

Liu D, Song Z, Wang X, Ouyang L (2020) Ubiquitin C-terminal hydrolase L5 (UCHL5) accelerates the growth of endometrial cancer via activating the Wnt/beta-Catenin signaling pathway. Front Oncol 10:865PubMedPubMedCentralCrossRef

Liu ZL, Bian M, Pang L (2022) LncRNA CRNDE deteriorates delayed encephalopathy after acute carbon monoxide poisoning to inactivate AKT/GSK3beta/beta-catenin pathway via miR-212-5p. Neurotox Res 40:1208–1222PubMedCrossRef

Lo CP, Chen SY, Lee KW, Chen WL, Chen CY, Hsueh CJ, Huang GS (2007) Brain injury after acute carbon monoxide poisoning: early and late complications. AJR Am J Roentgenol 189:W205-211PubMedCrossRef

Luo X, Tu T, Zhong Y, Xu S, Chen X, Chen L, Yang F (2021) ceRNA network analysis shows that lncRNA CRNDE promotes progression of glioblastoma through sponge mir-9-5p. Front Genet 12:617350PubMedPubMedCentralCrossRef

Ma X, Jin W, Zhao C, Wang X, Wang K (2022) CRNDE: A valuable long noncoding RNA for diagnosis and therapy of solid and hematological malignancies. Mol Ther Nucleic Acids 28:190–201PubMedPubMedCentralCrossRef

Meyer KD, Jaffrey SR (2014) The dynamic epitranscriptome: N6-methyladenosine and gene expression control. Nat Rev Mol Cell Biol 15:313–326PubMedPubMedCentralCrossRef

Nguyen V, Sabeur K, Maltepe E, Ameri K, Bayraktar O, Rowitch DH (2018) Sonic Hedgehog agonist protects against complex neonatal cerebellar injury. Cerebellum 17:213–227PubMedCrossRef

Nguyen V, Chavali M, Larpthaveesarp A, Kodali S, Gonzalez G, Franklin RJM, Rowitch DH, Gonzalez F (2021) Neuroprotective effects of Sonic hedgehog agonist SAG in a rat model of neonatal stroke. Pediatr Res 90:1161–1170PubMedPubMedCentralCrossRef

Ni W, Zhang Y, Zhan Z, Ye F, Liang Y, Huang J, Chen K, Chen L, Ding Y (2017) A novel lncRNA uc.134 represses hepatocellular carcinoma progression by inhibiting CUL4A-mediated ubiquitination of LATS1. J Hematol Oncol 10:91PubMedPubMedCentralCrossRef

Pringle AK, Solomon E, Coles BJ, Desousa BR, Shtaya A, Gajavelli S, Dabab N, Zaben MJ, Bulters DO, Bullock MR, Ahmed AI (2021) Sonic Hedgehog signaling promotes Peri-lesion cell proliferation and functional improvement after cortical contusion injury. Neurotrauma Rep 2:27–38PubMedPubMedCentralCrossRef

Qin S, Sun D, Zhang C, Tang Y, Zhou F, Zheng K, Tang R, Zheng Y (2019) Downregulation of sonic hedgehog signaling in the hippocampus leads to neuronal apoptosis in high-fat diet-fed mice. Behav Brain Res 367:91–100PubMedCrossRef

Qin L, Min S, Shu L, Pan H, Zhong J, Guo J, Sun Q, Yan X, Chen C, Tang B, Xu Q (2020) Genetic analysis of N6-methyladenosine modification genes in Parkinson’s disease. Neurobiol Aging 93:143 e149-143 e113CrossRef

Rahi S, Mehan S (2020) Understanding abnormal SMO-SHH signaling in autism spectrum disorder: potential drug target and therapeutic goals. Cell Mol Neurobiol

Ramaswami M, Taylor JP, Parker R (2013) Altered ribostasis: RNA-protein granules in degenerative disorders. Cell 154:727–736PubMedCrossRef

Rose JJ, Wang L, Xu Q, McTiernan CF, Shiva S, Tejero J, Gladwin MT (2017) Carbon monoxide poisoning: pathogenesis, management, and future directions of therapy. Am J Respir Crit Care Med 195:596–606PubMedPubMedCentralCrossRef

Roundtree IA, Evans ME, Pan T, He C (2017) Dynamic RNA modifications in gene expression regulation. Cell 169:1187–1200PubMedPubMedCentralCrossRef

Sharma A, Liu H, Tobar-Tosse F, Chand Dakal T, Ludwig M, Holz FG, Loeffler KU, Wullner U, Herwig-Carl MC (2020) Ubiquitin Carboxyl-Terminal Hydrolases (UCHs): potential mediators for cancer and neurodegeneration. Int J Mol Sci 21

Shruthi K, Reddy SS, Reddy PY, Shivalingam P, Harishankar N, Reddy GB (2016) Amelioration of neuronal cell death in a spontaneous obese rat model by dietary restriction through modulation of ubiquitin proteasome system. J Nutr Biochem 33:73–81PubMedCrossRef

Wang Y, Wang Y, Li J, Zhang Y, Yin H, Han B (2015) CRNDE, a long-noncoding RNA, promotes glioma cell growth and invasion through mTOR signaling. Cancer Lett 367:122–128PubMedCrossRef

Wang JP, Li C, Ding WC, Peng G, Xiao GL, Chen R, Cheng Q (2022) Research progress on the inflammatory effects of long non-coding RNA in traumatic brain injury. Front Mol Neurosci 15:835012PubMedPubMedCentralCrossRef

Xiao X, Yuan Z, Guo L, Liao X, Zhou Y, Zhang W, Zhou L, Wang X, Liu X, Liu H, Wang J, Li J, Shen L, Jiao B (2021) The role of frontotemporal dementia associated genes in patients with Alzheimer’s disease. Neurobiol Aging 107:153–158PubMedCrossRef

Xu K, Mo Y, Li D, Yu Q, Wang L, Lin F, Kong C, Balelang MF, Zhang A, Chen S, Dai Q, Wang J (2020) N(6)-methyladenosine demethylases Alkbh5/Fto regulate cerebral ischemia-reperfusion injury. Ther Adv Chronic Dis 11:2040622320916024PubMedPubMedCentralCrossRef

Yang LR, Lin ZY, Hao QG, Li TT, Zhu Y, Teng ZW, Zhang J (2022) The prognosis biomarkers based on m6A-related lncRNAs for myeloid leukemia patients. Cancer Cell Int 22:10PubMedPubMedCentralCrossRef

Yao W, Han X, Ge M, Chen C, Xiao X, Li H, Hei Z (2020) N(6)-methyladenosine (m(6)A) methylation in ischemia-reperfusion injury. Cell Death Dis 11:478PubMedPubMedCentralCrossRef

Zhang J, Yin M, Peng G, Zhao Y (2018) CRNDE: An important oncogenic long non-coding RNA in human cancers. Cell Prolif 51:e12440PubMedPubMedCentralCrossRef

Zhang D, Mou JY, Wang F, Liu J, Hu X (2019) CRNDE enhances neuropathic pain via modulating miR-136/IL6R axis in CCI rat models. J Cell Physiol 234:22234–22241PubMedCrossRef

Zhang J, Guo Y, Li W, Li G, Chen Y (2020) The efficacy of N-Butylphthalide and Dexamethasone combined with hyperbaric oxygen on delayed encephalopathy after acute carbon monoxide poisoning. Drug Des Devel Ther 14:1333–1339PubMedPubMedCentralCrossRef

Zhao BS, Roundtree IA, He C (2017) Post-transcriptional gene regulation by mRNA modifications. Nat Rev Mol Cell Biol 18:31–42PubMedCrossRef

Zhao F, Xu Y, Gao S, Qin L, Austria Q, Siedlak SL, Pajdzik K, Dai Q, He C, Wang W, O’Donnell JM, Tang B, Zhu X (2021) METTL3-dependent RNA m(6)A dysregulation contributes to neurodegeneration in Alzheimer’s disease through aberrant cell cycle events. Mol Neurodegener 16:70PubMedPubMedCentralCrossRef

Zhou Z, Yao X, Pang S, Chen P, Jiang W, Shan Z, Zhang Q (2018) The deubiquitinase UCHL5/UCH37 positively regulates Hedgehog signaling by deubiquitinating Smoothened. J Mol Cell Biol 10:243–257PubMedCrossRef

Zimmer-Bensch G (2019) Emerging roles of long non-coding RNAs as drivers of brain evolution. Cells 8

Titel: LncRNA CRNDE binds hnRNPA1 to facilitate carbon monoxide poisoning-induced delayed encephalopathy via inhibiting UCHL5-mediated SMO deubiquitination
verfasst von: Zuolong Liu
Miao Bian
Li Pang
Publikationsdatum: 17.01.2023
Verlag: Springer US
Erschienen in: Metabolic Brain Disease / Ausgabe 3/2023
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-022-01157-4

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