MALAT1 via microRNA-17 regulation of insulin transcription is involved in the dysfunction of pancreatic β-cells induced by cigarette smoke extract.
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.
['Sun|Qian|Q|', 'Xu|Hui|H|', 'Xue|Junchao|J|', 'Yang|Qianlei|Q|', 'Chen|Chao|C|', 'Yang|Ping|P|', 'Han|Aohan|A|', 'Tu|Qingyun|Q|', 'Lu|Jiachun|J|', 'Gao|Xiaohua|X|', 'Xiang|Quanyong|Q|', 'Liu|Qizhan|Q|0000-0001-6107-9232']
D000077192:Adenocarcinoma of Lung D017209:Apoptosis D002352:Carrier Proteins D002471:Cell Transformation, Neoplastic D000073865:Cigarette Smoking D003920:Diabetes Mellitus D015972:Gene Expression Regulation, Neoplastic D055785:Gene Knockdown Techniques D006442:Glycated Hemoglobin A D006801:Humans D007328:Insulin D007333:Insulin Resistance D050417:Insulin-Secreting Cells D035683:MicroRNAs D062085:RNA, Long Noncoding D015398:Signal Transduction D062789:Tobacco Products
smoking diabetes cigarette smoke extract (CSE) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) microRNA (miR)-17