Long, Noncoding RNA SRA Induces Apoptosis of beta-Cells by Promoting the IRAK1/LDHA/Lactate Pathway

doi:10.3390/ijms22041720

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/23511

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/23511

Title:	Long, Noncoding RNA SRA Induces Apoptosis of beta-Cells by Promoting the IRAK1/LDHA/Lactate Pathway
Authors:	Huang, YN;Chiang, SL;Lin, YJ;Liu, SC;Li, YH;Liao, YC;Lee, MR;Su, PH;Tsai, FJ;Hung, HC;Wang, CH
Keywords:	LncRNA SRA;LDHA;lactate;β -cell;type 1 diabetes mellitus
Date:	2021
Issue Date:	2022-08-05T09:38:28Z (UTC)
Publisher:	MDPI
Abstract:	Long non-coding RNA steroid receptor RNA activators (LncRNA SRAs) are implicated in the beta-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 beta-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 beta-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 beta-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 beta-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 beta-cells.
URI:	http://dx.doi.org/10.3390/ijms22041720 https://www.webofscience.com/wos/woscc/full-record/WOS:000623779100001 https://ir.csmu.edu.tw:8080/handle/310902500/23511
Relation:	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES ,2021,v22,issue 4
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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