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DOI: 10.1055/a-2077-5177
LncRNA LINC01018 Screens Type 2 Diabetes Mellitus and Regulates β Cell Function Through Modulating miR-499a-5p
Abstract
Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia, which seriously endangers human health. The dysregulation of lncRNA LINC01018 in T2DM has been noticed in previous studies, but whether it served as a biomarker lacks validation. This study aimed to confirm the abnormal expression of LINC01018 in T2DM and reveals its specific function in regulating pancreatic β cell function. This study enrolled 77 T2DM patients and 41 healthy individuals and compared the plasma LINC01018 levels between two groups using PCR. The pancreatic β cell was induced with 25 mM glucose to mimic cell injury during T2DM. The effects of LINC01018 on β cell proliferation, dedifferentiation, and insulin production were evaluated by CCK8, western blotting, and ELISA. Moreover, the involvement of miR-499a-5p was also evaluated with luciferase reporter assay. Increased plasma LINC01018 was observed in T2DM patients compared with healthy individuals, which discriminates patients with high sensitivity and specificity. Upregulated LINC01018 was associated with patients’ fasting blood glucose and weight loss. High glucose induced the increasing LINC01018 in pancreatic islet β cells and suppressed cell proliferation, insulin secretion, and promoted cell dedifferentiation. Silencing LINC01018 could alleviate the impaired function of β cells by high glucose, which was reversed by the knockdown by miR-499a-5p. Upregulated LINC01018 served as a potential diagnostic biomarker for T2DM and alleviated high glucose-induced β cell dysfunction via negatively modulating miR-499a-5p.
Key words
lncRNA - diagnostic biomarker - β cell - proliferation - dedifferentiation - insulin secretion, diabetesPublikationsverlauf
Eingereicht: 16. Februar 2023
Angenommen nach Revision: 12. April 2023
Artikel online veröffentlicht:
15. Mai 2023
© 2023. Thieme. All rights reserved.
Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany
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References
- 1 Izzo A, Massimino E, Riccardi G. et al. A narrative review on sarcopenia in type 2 diabetes mellitus: prevalence and associated factors. Nutrients 2021; 13: 183
- 2 Yan Y, Wu T, Zhang M. et al. Prevalence, awareness and control of type 2 diabetes mellitus and risk factors in Chinese elderly population. BMC Public Health 2022; 22: 1382
- 3 Kassi E, Pervanidou P, Kaltsas G. et al. Metabolic syndrome: definitions and controversies. BMC medicine 2011; 9: 48
- 4 Marušić M, Paić M, Knobloch M. et al. NAFLD, insulin resistance, and diabetes mellitus type 2. Can J Gastroenterol Hepatol 2021; 2021: 6613827
- 5 Rakshit K, Thomas AP, Matveyenko AV.. Does disruption of circadian rhythms contribute to beta-cell failure in type 2 diabetes?. Curr Diabetes Rep 2014; 14: 474
- 6 Kim H, Kulkarni RN.. Epigenetics in β-cell adaptation and type 2 diabetes. Curr Opin Pharmacol 2020; 55: 125-131
- 7 Wentzel A, Patterson AC, Duhuze Karera MG. et al. Non-invasive type 2 diabetes risk scores do not identify diabetes when the cause is β-cell failure: the Africans in America study. Front Public Health 2022; 10: 941086
- 8 Wang Z, York NW, Nichols CG. et al. Pancreatic β cell dedifferentiation in diabetes and redifferentiation following insulin therapy. Cell Metab 2014; 19: 872-882
- 9 Rutter GA, Pullen TJ, Hodson DJ. et al. Pancreatic β-cell identity, glucose sensing and the control of insulin secretion. Biochem J 2015; 466: 203-218
- 10 Cinti F, Bouchi R, Kim-Muller JY. et al. Evidence of β-cell dedifferentiation in human type 2 diabetes. J Clin Endocrinol Metab 2016; 101: 1044-1054
- 11 Bensellam M, Jonas JC, Laybutt DR.. Mechanisms of β-cell dedifferentiation in diabetes: recent findings and future research directions. J Endocrinol 2018; 236: R109-R143
- 12 Talchai C, Xuan S, Lin HV. et al. Pancreatic β cell dedifferentiation as a mechanism of diabetic β cell failure. Cell 2012; 150: 1223-1234
- 13 Sardu C, De Lucia C, Wallner M. et al. Diabetes mellitus and its cardiovascular complications: new insights into an old disease. J Diabetes Res 2019; 1905194
- 14 Yu T, Xu B, Bao M. et al. Identification of potential biomarkers and pathways associated with carotid atherosclerotic plaques in type 2 diabetes mellitus: a transcriptomics study. Front Endocrinol (Lausanne) 2022; 13: 981100
- 15 Su H, Hailin Z, Dongdong L. et al. Long non-coding RNA LINC01018 inhibits human glioma cell proliferation and metastasis by directly targeting miRNA-182-5p. J Neurooncol 2022; 160: 67-78
- 16 Wang S, Xu M, Sun Z. et al. LINC01018 confers a novel tumor suppressor role in hepatocellular carcinoma through sponging microRNA-182-5p. Am J Physiol Gastrointest Liver Physiol 2019; 317: G116-G126
- 17 Xu J, Wang J, Zhao M. et al. LncRNA LINC01018/miR-942-5p/KNG1 axis regulates the malignant development of glioma in vitro and in vivo. CNS Neurosci Therap 2023; 29: 691-711
- 18 Zhou H, Shi P, Jia X. et al. Long non-coding RNA LINC01018 inhibits the progression of acute myeloid leukemia by targeting miR-499a-5p to regulate PDCD4. Oncol Lett 2021; 22: 541
- 19 Zhou J, Zhang S, Sun X. et al. Hyperoside protects HK-2 cells against high glucose-induced apoptosis and inflammation via the miR-499a-5p/NRIP1 pathway. Pathol Oncol Res 2021; 27: 629829
- 20 Liu J, Huang L, Su P. et al. MicroRNA-499a-5p inhibits osteosarcoma cell proliferation and differentiation by targeting protein phosphatase 1D through protein kinase B/glycogen synthase kinase 3β signaling. Oncol Lett 2018; 15: 4113-4120
- 21 Neshati V, Mollazadeh S, Fazly Bazzaz BS. et al. MicroRNA-499a-5p Promotes differentiation of human bone marrow-derived mesenchymal stem cells to cardiomyocytes. Appl Biochem Biotechnol 2018; 186: 245-255
- 22 Chen Q, He Y, Wang X. et al. LncRNA PTGS2 regulates islet beta-cell function through the miR-146a-5p/RBP4 axis and its diagnostic value in type 2 diabetes mellitus. Am J Transl Res 2021; 13: 11316-11328
- 23 Aladel A, Verma AK, Dabeer S. et al. Association of lncRNA LINC01173 expression with vitamin-D and vitamin B12 level among type 2 diabetes patients. Diabetes Metab Syndr Obes 2022; 15: 2535-2543
- 24 Su M, Yu T, Yu Y. et al. hsa-miR-607, lncRNA TUG1 and hsa_circ_0071106 can be combined as biomarkers in type 2 diabetes mellitus. Exp Biol Med (Maywood) 2022; 247: 1609-1618
- 25 Eizirik DL, Pasquali L, Cnop M.. Pancreatic β-cells in type 1 and type 2 diabetes mellitus: different pathways to failure. Nat Rev Endocrinol 2020; 16: 349-362
- 26 Christensen AA, Gannon M.. The beta cell in type 2 diabetes. Curr Diabetes Rep. 2019; 19: 81
- 27 Zheng L, Wang Y, Li Y. et al. miR-765 targeting PDX1 impairs pancreatic beta-cell function to induce type 2 diabetes. Arch Physiol Biochem 2021; 1-10
- 28 Gu X, Dong M, Liu Z. et al. MiR-499a-5p Inhibits proliferation, invasion, migration, and epithelial-mesenchymal transition, and enhances radiosensitivity of cervical cancer cells via targeting eIF4E. Onco Targets Therapy 2020; 13: 2913-2924
- 29 He S, Li Z, Yu Y. et al. Exosomal miR-499a-5p promotes cell proliferation, migration and EMT via mTOR signaling pathway in lung adenocarcinoma. Exp Cell Res 2019; 379: 203-213
- 30 Ouyang L, Liu RD, Lei DQ. et al. MiR-499a-5p promotes 5-FU resistance and the cell proliferation and migration through activating PI3K/Akt signaling by targeting PTEN in pancreatic cancer. Ann Transl Med 2021; 9: 1798