Background: Type 1 diabetes (T1DM) severely threatens human health, and the dysfunction of insulin-secreting beta cells in islets is related to the reduced PDX-1 expression. It has been reported that long non-coding RNA MALAT1 regulates beta cell function, while the potential mechanism is unclear. Methods: Islets were isolated from non-obese diabetic (NOD) mice and wild type (WT) mice. Mouse islets and beta cell line (Min6) were stimulated by IL-1 beta. The expression of MALAT1 was determined using real-time PCR, while the PDX-1 protein expression was determined using western blotting. ChIP-qPCR was carried out to determine the histone acetylation of the PDX-1 promoter. Results: In NOD islets and IL-1 beta-stimulated Min6 cells, the expression of MALAT1 was increased, while the mRNA and protein levels of PDX-1 were decreased at an age/time-dependent manner. Overexpressing MALAT1 suppressed the H3 histone acetylation of the PDX-1 promoter, inhibiting both mRNA and protein expressions of PDX-1. Knocking down MALAT1 restored the decrease of the histone acetylation of the PDX-1 promoter, as well as the PDX-1 expression, which was reduced by IL-1 beta stimulation. Under high glucose stimulation, the overexpression of PDX-1 alone restored the insulin secretion which was inhibited by the simultaneous overexpression of MALAT1 and PDX-1. Under high glucose and IL-1 beta stimulation, the simultaneous knockdown of MALAT1 and PDX-1 reduced the enhancement of the insulin secretion which was raised by knocking down MALAT1 alone. Conclusion: MALAT1 induces the dysfunction of beta cells via reducing the H3 histone acetylation of the PDX-1 promoter and subsequently inhibiting the expression of PDX-1, thus suppressing the insulin secretion.
第一作者机构：[1]Hebei Med Univ, Hosp 4, Dept Endocrinol, 12 Jiankang Rd, Shijiazhuang 050000, Hebei, Peoples R China
通讯作者：
通讯机构：[1]Hebei Med Univ, Hosp 4, Dept Endocrinol, 12 Jiankang Rd, Shijiazhuang 050000, Hebei, Peoples R China[*1]Department of Endocrinology, The Fourth Hospital of Hebei Medical University, No. 12 Jiankang Road, Shijiazhuang 050000, China
推荐引用方式(GB/T 7714)：
Ding Haixia,Wang Fujun,Shi Xuelian,et al.LncRNA MALAT1 induces the dysfunction of beta cells via reducing the histone acetylation of the PDX-1 promoter in type 1 diabetes[J].EXPERIMENTAL AND MOLECULAR PATHOLOGY.2020,114:doi:10.1016/j.yexmp.2020.104432.
APA：
Ding, Haixia,Wang, Fujun,Shi, Xuelian,Ma, Hongfang,Du, Yaping...&Xing, Na.(2020).LncRNA MALAT1 induces the dysfunction of beta cells via reducing the histone acetylation of the PDX-1 promoter in type 1 diabetes.EXPERIMENTAL AND MOLECULAR PATHOLOGY,114,
MLA：
Ding, Haixia,et al."LncRNA MALAT1 induces the dysfunction of beta cells via reducing the histone acetylation of the PDX-1 promoter in type 1 diabetes".EXPERIMENTAL AND MOLECULAR PATHOLOGY 114.(2020)
