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长非编码RNA X-无活性特异转录 (lncRNA XIST) 通过竞争性结合microRNA-182-5p来抑制肝脏的胰岛素耐药性

Guoqing Zhong¹, Qingping Yang², Yihua Wang²

¹Hepatology Department, First People's Hospital, Nanyang, China.

Immunity, inflammation and disease

|November 29, 2023

概括

长非编码RNA (lncRNA) XIST通过调节miR-182-5p/IGF-1R轴和PI3K/Akt通路来减轻胰岛素抵抗 (IR). 这项研究确定了lncRNA XIST作为肝脏IR的潜在治疗点.

科学领域:

分子生物学分子生物学
遗传学遗传学是一个
内分泌学在内分泌学.

背景情况:

胰岛素抵抗 (IR) 是一种复杂的代谢障碍,其特征是胰岛素信号受损.
长非编码RNAs (lncRNAs) 在调节基因表达和细胞功能方面发挥着至关重要的作用.
在肝脏IR中lncRNA XIST的特定作用仍未完全阐明.

研究的目的:

在实验室中研究lncRNA XIST在肝脏胰岛素抵抗 (IR) 中的作用和分子机制.
在IR的背景下探索lncRNA XIST,miR-182-5p和IGF-1R之间的相互作用.
确定lncRNA XIST/miR-182-5p轴作为IR治疗点的潜力.

主要方法:

使用LX-2细胞建立一个体外IR模型.
基因和蛋白质表达水平的量化使用qRT-PCR和西方布洛特.
检测葡萄糖吸收和信号通路的激活.
使用生物信息学和分子测试,对分子相互作用进行预测和实验验证.
救援实验证实了miR-182-5p.p.的功能作用.

主要成果:

在LncRNA XIST表达下调,而miR-182-5p在IR细胞上调.
通过增加IGF-1R和葡萄糖吸收,增加了胰岛素敏感性,同时降低了葡萄糖生成酶 (G6Pase,PEPCK) 和激活PI3K/Akt通路.
LncRNA XIST 作为 miR-182-5p 的分子海绵,miR-182-5p 直接准了 IGF-1R.
模仿米R-182-5p可以逆转 lncRNA XIST 过度表达对红外细胞的影响.

结论:

lncRNA XIST/miR-182-5p轴在缓解肝脏IR.中发挥着至关重要的作用.
这个轴通过调节IGF-1R/PI3K/Akt信号通路来发挥作用.
针对lncRNA XIST/miR-182-5p轴是一个有前途的治疗策略,用于管理肝脏IR.

关键词:

胰岛素耐药性是一种胰岛素耐药性.胰岛素类生长因子-1受体 lncRNA X-无活性特异性转录在 miR-182-5p 中.

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