Long, Noncoding RNA SRA Induces Apoptosis of β-Cells by Promoting the IRAK1/LDHA/Lactate Pathway
Long non-coding RNA steroid receptor RNA activators (LncRNA SRAs) are implicated in the β-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 β-cells. LncRNA SRAs were highly expressed...
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doaj-df7f3453e8ed419986af956ef5b545612021-02-10T00:00:46ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01221720172010.3390/ijms22041720Long, Noncoding RNA SRA Induces Apoptosis of β-Cells by Promoting the IRAK1/LDHA/Lactate PathwayYu-Nan Huang0Shang-Lun Chiang1Yu-Jung Lin2Su-Ching Liu3Yen-Hsien Li4Yu-Chen Liao5Maw-Rong Lee6Pen-Hua Su7Fuu-Jen Tsai8Hui-Chih Hung9Chung-Hsing Wang10Department of Life Sciences, National Chung Hsing University, Taichung 402, TaiwanDepartment of Medical Laboratory Science, I-Shou University, Kaohsiung 824, TaiwanCardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, TaiwanDepartment of Medical Research, Children’s Hospital of China Medical University, Taichung 404, TaiwanDepartment of Chemistry, National Chung Hsing University, Taichung 420, TaiwanInstrument Center, Office of Research and Development, National Chung Hsing University, Taichung 420, TaiwanDepartment of Chemistry, National Chung Hsing University, Taichung 420, TaiwanDepartment of Pediatrics, Chung Shan Medical University Hospital, Taichung 412, TaiwanGenetic Center, Department of Medical Research, China Medical University Hospital, Taichung 40447, TaiwanDepartment of Life Sciences, National Chung Hsing University, Taichung 402, TaiwanDivision of Genetics and Metabolism, Children’s Hospital of China Medical University, Taichung 402, TaiwanLong non-coding RNA steroid receptor RNA activators (LncRNA SRAs) are implicated in the β-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 β-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 β-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 β-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 β-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 β-cells.https://www.mdpi.com/1422-0067/22/4/1720LncRNA SRALDHAlactateβ-celltype 1 diabetes mellitus |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yu-Nan Huang Shang-Lun Chiang Yu-Jung Lin Su-Ching Liu Yen-Hsien Li Yu-Chen Liao Maw-Rong Lee Pen-Hua Su Fuu-Jen Tsai Hui-Chih Hung Chung-Hsing Wang |
spellingShingle |
Yu-Nan Huang Shang-Lun Chiang Yu-Jung Lin Su-Ching Liu Yen-Hsien Li Yu-Chen Liao Maw-Rong Lee Pen-Hua Su Fuu-Jen Tsai Hui-Chih Hung Chung-Hsing Wang Long, Noncoding RNA SRA Induces Apoptosis of β-Cells by Promoting the IRAK1/LDHA/Lactate Pathway International Journal of Molecular Sciences LncRNA SRA LDHA lactate β-cell type 1 diabetes mellitus |
author_facet |
Yu-Nan Huang Shang-Lun Chiang Yu-Jung Lin Su-Ching Liu Yen-Hsien Li Yu-Chen Liao Maw-Rong Lee Pen-Hua Su Fuu-Jen Tsai Hui-Chih Hung Chung-Hsing Wang |
author_sort |
Yu-Nan Huang |
title |
Long, Noncoding RNA SRA Induces Apoptosis of β-Cells by Promoting the IRAK1/LDHA/Lactate Pathway |
title_short |
Long, Noncoding RNA SRA Induces Apoptosis of β-Cells by Promoting the IRAK1/LDHA/Lactate Pathway |
title_full |
Long, Noncoding RNA SRA Induces Apoptosis of β-Cells by Promoting the IRAK1/LDHA/Lactate Pathway |
title_fullStr |
Long, Noncoding RNA SRA Induces Apoptosis of β-Cells by Promoting the IRAK1/LDHA/Lactate Pathway |
title_full_unstemmed |
Long, Noncoding RNA SRA Induces Apoptosis of β-Cells by Promoting the IRAK1/LDHA/Lactate Pathway |
title_sort |
long, noncoding rna sra induces apoptosis of β-cells by promoting the irak1/ldha/lactate pathway |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1661-6596 1422-0067 |
publishDate |
2021-02-01 |
description |
Long non-coding RNA steroid receptor RNA activators (LncRNA SRAs) are implicated in the β-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 β-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 β-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 β-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 β-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 β-cells. |
topic |
LncRNA SRA LDHA lactate β-cell type 1 diabetes mellitus |
url |
https://www.mdpi.com/1422-0067/22/4/1720 |
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