MALAT1 via microRNA‐17 regulation of insulin transcription is involved in the dysfunction of pancreatic β‐cells induced by cigarette smoke extract

作者：Qian Sun, Hui Xu, Junchao Xue, Qianlei Yang, Chao Chen, Ping Yang, Aohan Han, Qingyun Tu, Jiachun Lü, Xiaohua Gao, Quanyong Xiang, Qizhan Liu · 发表于：Journal of Cellular Physiology · 年份：2018 · DOI：10.1002/jcp.26800 · 被引用次数：22 · 研究领域：Cancer-related molecular mechanisms research、MicroRNA in disease regulation、Adipose Tissue and Metabolism

Cigarettes contain various chemicals with the potential to influence metabolic health. Exposure to cigarette smoke causes a dysfunction in pancreatic β-cells and impairs insulin production. However, the mechanisms for cigarette smoke-induced reduction of insulin remain largely unclear. Data from 558 patients with diabetes showed that, with smoking pack-years, homeostatic model assessment (HOMA)-β (a method for assessing β-cell function) decreased and that HOMA of insulin resistance increased. For β-cells (MIN6), cigarette smoke extract (CSE) increased the levels of thioredoxin-interacting protein (TXNIP) and the long noncoding (lnc)RNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), and downregulated the levels of the transcription factor, mafA, and microRNA (miR)-17. MALAT1, one of four lncRNAs predicted to regulate miR-17, was knocked down by small interfering RNA (siRNA). For these cells, an miR-17 mimic inhibited TXNIP and enhanced the production of insulin. Knockdown of MALAT1 induced an increase in miR-17, which suppressed TXNIP and promoted the production of insulin. In the sera of patients with diabetes who smoked, there were higher MALAT1 levels and lower miR-17 levels than in the sera of nonsmokers. Thus, CSE inhibits insulin production by upregulating TXNIP via MALAT1-mediated downregulation of miR-17, which provides an understanding of the processes involved in the reduced β-cells function caused by cigarette smoke.