XIST and MUC1-C form an auto-regulatory pathway in driving cancer progression.
Cell Death Dis
; 15(5): 330, 2024 May 13.
Article
em En
| MEDLINE
| ID: mdl-38740827
ABSTRACT
The long non-coding RNA X-inactive specific transcript (lncRNA XIST) and MUC1 gene are dysregulated in chronic inflammation and cancer; however, there is no known interaction of their functions. The present studies demonstrate that MUC1-C regulates XIST lncRNA levels by suppressing the RBM15/B, WTAP and METTL3/14 components of the m6A methylation complex that associate with XIST A repeats. MUC1-C also suppresses the YTHDF2-CNOT1 deadenylase complex that recognizes m6A sites and contributes to XIST decay with increases in XIST stability and expression. In support of an auto-regulatory pathway, we show that XIST regulates MUC1-C expression by promoting NF-κB-mediated activation of the MUC1 gene. Of significance, MUC1-C and XIST regulate common genes associated with inflammation and stemness, including (i) miR-21 which is upregulated across pan-cancers, and (ii) TDP-43 which associates with the XIST E repeats. Our results further demonstrate that the MUC1-C/XIST pathway (i) is regulated by TDP-43, (ii) drives stemness-associated genes, and (iii) is necessary for self-renewal capacity. These findings indicate that the MUC1-C/XIST auto-regulatory axis is of importance in cancer progression.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Regulação Neoplásica da Expressão Gênica
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Mucina-1
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RNA Longo não Codificante
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article