{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:17:02Z","timestamp":1791919022178,"version":"4.3.4"},"reference-count":44,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T00:00:00Z","timestamp":1612828800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 106-2314-B-039-024-MY2 and MOST 109-2314-B-039-035"],"award-info":[{"award-number":["MOST 106-2314-B-039-024-MY2 and MOST 109-2314-B-039-035"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004391","name":"China Medical University Hospital","doi-asserted-by":"publisher","award":["DMR-106-051, DMR-107-053, DMR-108-040 and DMR-108-042"],"award-info":[{"award-number":["DMR-106-051, DMR-107-053, DMR-108-040 and DMR-108-042"]}],"id":[{"id":"10.13039\/501100004391","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Long non-coding RNA steroid receptor RNA activators (LncRNA SRAs) are implicated in the \u03b2-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 \u03b2-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\u2013structure 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 \u03b2-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 \u03b2-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 \u03b2-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 \u03b2-cells.<\/jats:p>","DOI":"10.3390\/ijms22041720","type":"journal-article","created":{"date-parts":[[2021,2,9]],"date-time":"2021-02-09T23:43:16Z","timestamp":1612914196000},"page":"1720","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Long, Noncoding RNA SRA Induces Apoptosis of \u03b2-Cells by Promoting the IRAK1\/LDHA\/Lactate Pathway"],"prefix":"10.3390","volume":"22","author":[{"given":"Yu-Nan","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan"},{"name":"Division of Genetics and Metabolism, Children\u2019s Hospital of China Medical University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shang-Lun","family":"Chiang","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science, I-Shou University, Kaohsiung 824, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5757-1021","authenticated-orcid":false,"given":"Yu-Jung","family":"Lin","sequence":"additional","affiliation":[{"name":"Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Ching","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Children\u2019s Hospital of China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Hsien","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Chung Hsing University, Taichung 420, Taiwan"},{"name":"Instrument Center, Office of Research and Development, National Chung Hsing University, Taichung 420, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chen","family":"Liao","sequence":"additional","affiliation":[{"name":"Instrument Center, Office of Research and Development, National Chung Hsing University, Taichung 420, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maw-Rong","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Chemistry, National Chung Hsing University, Taichung 420, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pen-Hua","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Chung Shan Medical University Hospital, Taichung 412, Taiwan"},{"name":"School of Medicine, Chung Shan Medical University, Taichung City 40201, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuu-Jen","family":"Tsai","sequence":"additional","affiliation":[{"name":"Genetic Center, Department of Medical Research, China Medical University Hospital, Taichung 40447, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0180-1822","authenticated-orcid":false,"given":"Hui-Chih","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, National Chung Hsing University, Taichung 402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Hsing","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Children\u2019s Hospital of China Medical University, Taichung 402, Taiwan"},{"name":"School of Medicine, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"American Diabetes Association (2018). 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