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miRNA-16-5p inhibits the apoptosis of high glucose-induced pancreatic β cells via targeting of CXCL10: potential biomarkers in type 1 diabetes mellitus
Affiliations- Department of Internal Medicine, Tianqiao District People's Hospital of Ji'nan City, Jin'an City, Shandong Province, China
- Department of Endocrinology, The Fifth's People's Hospital of Ji'nan City, Ji'nan City, Shandong Province, China
open access
Abstract
Introduction: We aimed to elucidate the relationship between CXC chemokine ligand 10 (CXCL10) and miR-16-5p, and their functions on the biological behaviour of type 1 diabetes mellitus (T1DM).
Material and methods: The GSE72492 dataset from the GEO database was used to analyse gene expression. We discovered that CXCL10 was highly expressed in T1DM patients. The up-stream miRNA was predicted by Targetscan website. Low glucose (2.8 mmol/L) and high glucose (HG, 16.7 mmol/L) were utilised to treat β-TC-tet (pancreatic β cell) cells to form the model. The direct interaction between miR-16-5p and CXCL10 was verified by a dual-luciferase reporter assay. Real-time quantitative PCR (qRT-PCR) and western blotting analyses were used to detect RNA and protein expression. CCK8 and flow cytometry were used to detect cell proliferation and apoptosis.
Results: We discovered that CXCL10 was highly expressed in T1DM patients. MiR-16-5p, which was lowly expressed in T1DM patients, was verified the upstream regulatory miRNA of CXCL10. The facilitating influence of miR-16-5p up-regulation on the proliferation of HG-induced β-TC-tet cells was reversed by CXCL10 over-expression, while the knockdown results were opposite. More importantly, the restraining impact of miR-16-5p high expression on the apoptosis of HG-induced β-TC-tet cells was accelerated by CXCL10 over-expression. Correspondingly, the level of Bcl-2 was enhanced while the levels of Bax and Cleaved Caspase-3 were lowered by miR-16-5p mimic, which were reversed by CXCL10 over-expression in HG-treated β-TC-tet cells.
Conclusions: Our data offered evidence that miR-16-5p implicated in T1DM cell proliferation and apoptosis through targeting CXCL10, which might provide novel therapeutic information for T1DM.
Abstract
Introduction: We aimed to elucidate the relationship between CXC chemokine ligand 10 (CXCL10) and miR-16-5p, and their functions on the biological behaviour of type 1 diabetes mellitus (T1DM).
Material and methods: The GSE72492 dataset from the GEO database was used to analyse gene expression. We discovered that CXCL10 was highly expressed in T1DM patients. The up-stream miRNA was predicted by Targetscan website. Low glucose (2.8 mmol/L) and high glucose (HG, 16.7 mmol/L) were utilised to treat β-TC-tet (pancreatic β cell) cells to form the model. The direct interaction between miR-16-5p and CXCL10 was verified by a dual-luciferase reporter assay. Real-time quantitative PCR (qRT-PCR) and western blotting analyses were used to detect RNA and protein expression. CCK8 and flow cytometry were used to detect cell proliferation and apoptosis.
Results: We discovered that CXCL10 was highly expressed in T1DM patients. MiR-16-5p, which was lowly expressed in T1DM patients, was verified the upstream regulatory miRNA of CXCL10. The facilitating influence of miR-16-5p up-regulation on the proliferation of HG-induced β-TC-tet cells was reversed by CXCL10 over-expression, while the knockdown results were opposite. More importantly, the restraining impact of miR-16-5p high expression on the apoptosis of HG-induced β-TC-tet cells was accelerated by CXCL10 over-expression. Correspondingly, the level of Bcl-2 was enhanced while the levels of Bax and Cleaved Caspase-3 were lowered by miR-16-5p mimic, which were reversed by CXCL10 over-expression in HG-treated β-TC-tet cells.
Conclusions: Our data offered evidence that miR-16-5p implicated in T1DM cell proliferation and apoptosis through targeting CXCL10, which might provide novel therapeutic information for T1DM.
Keywords
type 1 diabetes mellitus; CXC chemokine ligand 10; miRNA-16-5p; target; relationship
About this articleTitle
miRNA-16-5p inhibits the apoptosis of high glucose-induced pancreatic β cells via targeting of CXCL10: potential biomarkers in type 1 diabetes mellitus
Journal
Issue
Article type
Original paper
Pages
404-410
Published online
2020-08-03
Page views
1611
Article views/downloads
939
DOI
Pubmed
Bibliographic record
Endokrynol Pol 2020;71(5):404-410.
Keywords
type 1 diabetes mellitus
CXC chemokine ligand 10
miRNA-16-5p
target
relationship
Authors
Xiaoyan Gao
Shumiao Zhao
References (34)- Yi Bo, Huang G, Zhou Z. Different role of zinc transporter 8 between type 1 diabetes mellitus and type 2 diabetes mellitus. J Diabetes Investig. 2016; 7(4): 459–465.
- Novotna M, Podzimek S, Broukal Z, et al. Periodontal Diseases and Dental Caries in Children with Type 1 Diabetes Mellitus. Mediators Inflamm. 2015; 2015: 379626.
- Rak K, Bronkowska M. Immunomodulatory Effect of Vitamin D and Its Potential Role in the Prevention and Treatment of Type 1 Diabetes Mellitus-A Narrative Review. Molecules. 2018; 24(1).
- Zhang L, Zhang Q. Glycated Plasma Proteins as More Sensitive Markers for Glycemic Control in Type 1 Diabetes. Proteomics Clin Appl. 2020; 14(2): e1900104.
- Chellappan DK, Sivam NS, Teoh KX, et al. Gene therapy and type 1 diabetes mellitus. Biomed Pharmacother. 2018; 108: 1188–1200.
- Fu S, Li L, Deng S, et al. Effectiveness of advanced carbohydrate counting in type 1 diabetes mellitus: a systematic review and meta-analysis. Sci Rep. 2016; 6: 37067.
- Bjerg L, Hulman A, Charles M, et al. Clustering of microvascular complications in Type 1 diabetes mellitus. J Diabetes Complications. 2018; 32(4): 393–399.
- Garcia-Contreras M, Brooks RW, Boccuzzi L, et al. Exosomes as biomarkers and therapeutic tools for type 1 diabetes mellitus. Eur Rev Med Pharmacol Sci. 2017; 21(12): 2940–2956.
- He J, Lian C, Fang Y, et al. Effect of CXCL10 receptor antagonist on islet cell apoptosis in a type I diabetes rat model. Int J Clin Exp Pathol. 2015; 8: 14542–14548.
- Lee JH, Kim B, Jin WJ, et al. Pathogenic roles of CXCL10 signaling through CXCR3 and TLR4 in macrophages and T cells: relevance for arthritis. Arthritis Res Ther. 2017; 19(1): 163.
- Fan Y, Zhang W, Wei H, et al. Hepatic NK cells attenuate fibrosis progression of non-alcoholic steatohepatitis in dependent of CXCL10-mediated recruitment. Liver Int. 2020; 40(3): 598–608.
- Antonelli A, Ferrari SM, Giuggioli D, et al. Chemokine (C-X-C motif) ligand (CXCL)10 in autoimmune diseases. Autoimmun Rev. 2014; 13(3): 272–280.
- Chen Ju, Ye X, Pitmon E, et al. IL-17 inhibits CXCL9/10-mediated recruitment of CD8 cytotoxic T cells and regulatory T cells to colorectal tumors. J Immunother Cancer. 2019; 7(1): 324.
- Homann D. Back From the Brink: The Uses of Targeting the CXCL10:CXCR3 Axis in Type 1 Diabetes. Diabetes. 2015; 64(12): 3990–3992.
- Ahmadi Z, Arababadi MK, Hassanshahi G. CXCL10 activities, biological structure, and source along with its significant role played in pathophysiology of type I diabetes mellitus. Inflammation. 2013; 36(2): 364–371.
- Pan W, Zhang Y, Zeng C, et al. miR-192 is upregulated in T1DM, regulates pancreatic β-cell development and inhibits insulin secretion through suppressing GLP-1 expression. Exp Ther Med. 2018; 16(3): 2717–2724.
- Lakhter AJ, Pratt RE, Moore RE, et al. Beta cell extracellular vesicle miR-21-5p cargo is increased in response to inflammatory cytokines and serves as a biomarker of type 1 diabetes. Diabetologia. 2018; 61(5): 1124–1134.
- Assmann TS, Recamonde-Mendoza M, De Souza BM, et al. MicroRNA expression profiles and type 1 diabetes mellitus: systematic review and bioinformatic analysis. Endocr Connect. 2017; 6(8): 773–790.
- Assmann TS, Recamonde-Mendoza M, Costa AR, et al. Circulating miRNAs in diabetic kidney disease: case-control study and in silico analyses. Acta Diabetol. 2019; 56(1): 55–65.
- Yue Y, Tang Y, Tang J, et al. Maternal infection during pregnancy and type 1 diabetes mellitus in offspring: a systematic review and meta-analysis. Epidemiol Infect. 2018; 146(16): 2131–2138.
- Herold KC, Vignali DAA, Cooke A, et al. Type 1 diabetes: translating mechanistic observations into effective clinical outcomes. Nat Rev Immunol. 2013; 13(4): 243–256.
- DiMeglio LA, Evans-Molina C, Oram RA. Type 1 diabetes. Lancet. 2018; 391(10138): 2449–2462.
- Antonelli A, Ferrari SM, Corrado A, et al. CXCR3, CXCL10 and type 1 diabetes. Cytokine Growth Factor Rev. 2014; 25(1): 57–65.
- Homann D. Back From the Brink: The Uses of Targeting the CXCL10:CXCR3 Axis in Type 1 Diabetes. Diabetes. 2015; 64(12): 3990–3992.
- Corrado A, Ferrari SM, Ferri C, et al. Type 1 diabetes and (C-X-C motif) ligand (CXCL) 10 chemokine. Clin Ter. 2014; 165(2): e181–e185.
- Christen S, Holdener M, Beerli C, et al. Small molecule CXCR3 antagonist NIBR2130 has only a limited impact on type 1 diabetes in a virus-induced mouse model. Clin Exp Immunol. 2011; 165(3): 318–328.
- Coppieters KT, Amirian N, Pagni PP, et al. Functional redundancy of CXCR3/CXCL10 signaling in the recruitment of diabetogenic cytotoxic T lymphocytes to pancreatic islets in a virally induced autoimmune diabetes model. Diabetes. 2013; 62(7): 2492–2499.
- Liu B, Shyr Yu, Cai J, et al. Interplay between miRNAs and host genes and their role in cancer. Brief Funct Genomics. 2018; 18(4): 255–266.
- Steiman-Shimony A, Shtrikman O, Margalit H. Assessing the functional association of intronic miRNAs with their host genes. RNA. 2018; 24(8): 991–1004.
- Liu Z, Wang Y, Wang L, et al. Long non-coding RNA AGAP2-AS1, functioning as a competitive endogenous RNA, upregulates ANXA11 expression by sponging miR-16-5p and promotes proliferation and metastasis in hepatocellular carcinoma. J Exp Clin Cancer Res. 2019; 38(1): 194.
- Schulthess FT, Paroni F, Sauter NS, et al. CXCL10 impairs beta cell function and viability in diabetes through TLR4 signaling. Cell Metab. 2009; 9(2): 125–139.
- Cai B, Ma M, Chen B, et al. MiR-16-5p targets SESN1 to regulate the p53 signaling pathway, affecting myoblast proliferation and apoptosis, and is involved in myoblast differentiation. Cell Death Dis. 2018; 9(3): 367.
- Sun Y, Xiong Y, Yan C, et al. Downregulation of microRNA-16-5p accelerates fracture healing by promoting proliferation and inhibiting apoptosis of osteoblasts in patients with traumatic brain injury. Am J Transl Res. 2019; 11(8): 4746–4760.
- Ren Yu, Huang W, Weng G, et al. LncRNA PVT1 promotes proliferation, invasion and epithelial-mesenchymal transition of renal cell carcinoma cells through downregulation of miR-16-5p. Onco Targets Ther. 2019; 12: 2563–2575.
