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Lin28a expression protects against streptozotocin-induced beta-cell destruction and prevents diabetes in mice

Title
Lin28a expression protects against streptozotocin-induced beta-cell destruction and prevents diabetes in mice
Authors
Sung, YonghunJeong, JainKang, Ri JinChoi, MinjeePark, SongKwon, WookbongLee, JinheeJang, SoyoungPark, Si JunKim, Sung-HyunYi, JunkooChoi, Seong-KyoonLee, Mee-HyunLiu, KangdongDong, ZigangRyoo, Zae YoungKim, Myoung Ok
DGIST Authors
Choi, Seong-Kyoon
Issue Date
2019-04
Citation
Cell Biochemistry and Function, 37(3), 139-147
Type
Article
Article Type
Article
Author Keywords
diabeteslet-7Lin28apancreatic beta-cellSTZ
Keywords
CANCER PROGRESSIONLET-7GROWTHSUSCEPTIBILITYMODULATIONBINDINGRNA
ISSN
0263-6484
Abstract
Lin28, which is highly expressed during embryogenesis, has been shown to play an important role in cell growth and embryonic development. Meanwhile, Lin28 represses let-7 miRNA biogenesis and block pre-let-7 processing in the cytoplasm. The let-7 family of miRNAs is known to repress oncogenesis and cell cycle progression by targeting oncogenic genes and signalling pathways. Consequently, Lin28 acts as an oncogene by upregulating let-7 targets through the repression of let-7 biogenesis. A recent genome-wide association study (GWAS) showed that many genes related to Type 2 diabetes (T2D) are also oncogenes or cell cycle regulators. The role of Lin28 in mouse growth and glucose metabolism in metabolic-related tissues has also been studied. In these studies, whole-body Lin28 overexpression was found to promote glucose utilization and prevent weight gain by inhibiting let-7 biogenesis. Furthermore, Lin28 has been found to directly stimulate skeletal myogenesis and cell growth. Therefore, we determined whether similar effects mediated by Lin28a, which is essential for cell growth and proliferation, may also apply to pancreatic ß-cells. We found that overexpression of Lin28a protects pancreatic β-cells from streptozotocin (STZ)-induced β-cell destruction in vitro and in vivo. Furthermore, Lin28a-overexpressing transgenic (Tg) mice had higher insulin secretion in the presence of glucose than in control mice. Our findings suggest that the Lin28/let-7 axis is an important regulator of pancreatic β-cell functions and that precise modulation of this axis may be helpful in treating metabolic diseases such as diabetes. Significance of the study: We demonstrate that Lin28a prevents pancreatic β-cell death against streptozotocin (STZ)-induced β-cell destruction in vitro and in vivo. Furthermore, Lin28a promotes cell survival and proliferation by activating the PI3K-Akt signalling pathway, which may be dependent on let-7 regulation. Taken together, our results imply that the Lin28a/let-7 axis is an important regulator of pancreatic β-cell functions and that precise modulation of this axis may be helpful in treating metabolic diseases such as diabetes. © 2019 John Wiley & Sons, Ltd.
URI
http://hdl.handle.net/20.500.11750/9822
DOI
10.1002/cbf.3376
Publisher
John Wiley & Sons Inc.
Related Researcher
Files:
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Collection:
Core Protein Resources Center1. Journal Articles


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