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Downregulation of Lnc-ABCA12-3 modulates UBQLN1 expression and protein homeostasis pathways in amyotrophic lateral sclerosis.
Yu, Yujiao; Pang, Dejiang; Huang, Jingxuan; Li, Chunyu; Cui, Yiyuan; Shang, Huifang.
Afiliação
  • Yu Y; Department of Neurology, Laboratory of Neurodegenerative Disorders, West China Hospital, National Clinical Research Center for Geriatrics, Sichuan University, No.37, Guoxue Lane, Chengdu, 610041, China.
  • Pang D; Department of Neurology, Laboratory of Neurodegenerative Disorders, West China Hospital, National Clinical Research Center for Geriatrics, Sichuan University, No.37, Guoxue Lane, Chengdu, 610041, China.
  • Huang J; Department of Neurology, Laboratory of Neurodegenerative Disorders, West China Hospital, National Clinical Research Center for Geriatrics, Sichuan University, No.37, Guoxue Lane, Chengdu, 610041, China.
  • Li C; Department of Neurology, Laboratory of Neurodegenerative Disorders, West China Hospital, National Clinical Research Center for Geriatrics, Sichuan University, No.37, Guoxue Lane, Chengdu, 610041, China.
  • Cui Y; Department of Neurology, Laboratory of Neurodegenerative Disorders, West China Hospital, National Clinical Research Center for Geriatrics, Sichuan University, No.37, Guoxue Lane, Chengdu, 610041, China.
  • Shang H; Department of Neurology, Laboratory of Neurodegenerative Disorders, West China Hospital, National Clinical Research Center for Geriatrics, Sichuan University, No.37, Guoxue Lane, Chengdu, 610041, China. hfshang2002@126.com.
Sci Rep ; 14(1): 21383, 2024 09 13.
Article em En | MEDLINE | ID: mdl-39271939
ABSTRACT
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron degeneration. Dysregulation of long non-coding RNAs (lncRNAs) has been implicated in ALS pathogenesis but their roles remain unclear. Previous studies found lnc-ABCA12-3 was downregulated in ALS patients. We aim to characterize the expression and function of lnc-ABCA12-3 in ALS and explore its mechanisms of action. Lnc-ABCA12-3 expression was analyzed in PBMCs from ALS patients and correlated with clinical outcomes. Effect of modulating lnc-ABCA12-3 expression was assessed in cell models using assays of apoptosis, protein homeostasis and pathway analysis. RNA pull-down and interaction studies were performed to identify lnc-ABCA12-3 binding partners. Lnc-ABCA12-3 was downregulated in ALS patients, correlating with faster progression and shorter survival. Overexpression of lnc-ABAC12-3 conferred protection against oxidative stress-induced apoptosis, while knockdown lnc-ABCA12-3 enhanced cell death. Lnc-ABCA12-3 maintained protein quality control pathways, including ubiquitination, autophagy and stress granule formation, by regulating the ubiquitin shuttle protein UBQLN1. This study identified lnc-ABCA12-3 as a novel regulatory lncRNA implicated in ALS pathogenesis by modulating cellular survival and stress responses through interactions with UBQLN1, influencing disease progression. Lnc-ABCA12-3 may influence ALS through regulating protein homeostasis pathways.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação para Baixo / Apoptose / Proteínas Adaptadoras de Transdução de Sinal / RNA Longo não Codificante / Proteínas Relacionadas à Autofagia / Esclerose Lateral Amiotrófica Limite: Female / Humans / Male / Middle aged Idioma: En Revista: Sci Rep Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Reino Unido
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Regulação para Baixo / Apoptose / Proteínas Adaptadoras de Transdução de Sinal / RNA Longo não Codificante / Proteínas Relacionadas à Autofagia / Esclerose Lateral Amiotrófica Limite: Female / Humans / Male / Middle aged Idioma: En Revista: Sci Rep Ano de publicação: 2024 Tipo de documento: Article País de afiliação: China País de publicação: Reino Unido