Long, Noncoding RNA SRA Induces Apoptosis of ß-Cells by Promoting the IRAK1/LDHA/Lactate Pathway.
Int J Mol Sci
; 22(4)2021 Feb 09.
Article
en En
| MEDLINE
| ID: mdl-33572095
ABSTRACT
Long non-coding RNA steroid receptor RNA activators (LncRNA SRAs) are implicated in the ß-cell destruction of Type 1 diabetes mellitus (T1D), but functional association remains poorly understood. Here, we aimed to verify the role of LncRNA SRA regulation in ß-cells. LncRNA SRAs were highly expressed in plasma samples and peripheral blood mononuclear cells (PBMCs) from T1D patients. LncRNA SRA was strongly upregulated by high-glucose treatment. LncRNA SRA acts as a microRNA (miR)-146b sponge through direct sequence-structure interactions. Silencing of lncRNA SRA increased the functional genes of Tregs, resulting in metabolic reprogramming, such as decreased lactate levels, repressed lactate dehydrogenase A (LDHA)/phosphorylated LDHA (pLDHA at Tyr10) expression, decreased reactive oxygen species (ROS) production, increased ATP production, and finally, decreased ß-cell apoptosis in vitro. There was a positive association between lactate level and hemoglobin A1c (HbA1c) level in the plasma from patients with T1D. Recombinant human interleukin (IL)-2 treatment repressed lncRNA SRA expression and activity in ß-cells. Higher levels of lncRNA-SRA/lactate in the plasma are associated with poor regulation in T1D patients. LncRNA SRA contributed to T1D pathogenesis through the inhibition of miR-146b in ß-cells, with activating signaling transduction of interleukin-1 receptor-associated kinase 1 (IRAK1)/LDHA/pLDHA. Taken together, LncRNA SRA plays a critical role in the function of ß-cells.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Portadoras
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MicroARNs
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Diabetes Mellitus Tipo 1
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Células Secretoras de Insulina
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ARN Largo no Codificante
Tipo de estudio:
Observational_studies
Límite:
Adolescent
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Adult
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Female
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Humans
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Male
Idioma:
En
Año:
2021
Tipo del documento:
Article