长非编码RNA CASC15影响肝细胞SREBP1a表达及定位

Long Non-coding RNA CASC15 Affects Expression and Localization of SREBP1a in Hepatocytes

长非编码RNA CASC15(long non-coding RNA CASC15,CASC15)被认为是一种与肿瘤相关的lncRNA,参与调控多种肿瘤的侵袭、增殖和迁移等生物学过程。然而CASC15在细胞内脂质代谢中的作用仍不明确。胆固醇调节元件结合蛋白1(SREBP1)是细胞内调控脂质代谢的关键转录因子,其成员SREBP1a主要调控脂肪合成中关键酶基因的表达。本文通过分子生物学实验及细胞功能学实验,研究CASC15对人肝细胞中脂质调控因子SREBP1a表达及定位的影响。研究结果显示,在肝细胞中,过表达CASC15(P<0.001)后细胞内的SREBP1a的mRNA和总蛋白质水平不变,前体蛋白质水平增加(P<0.05)且定位发生改变,即入核增加;SREBP1a调控脂肪酸合成相关产物游离脂肪酸(P<0.001)和甘油三酯(P<0.001)呈下调趋势。本文揭示了CASC15调控肝细胞脂代谢的一种可能机制,希望为脂代谢紊乱相关疾病的治疗和研究提供新思路。

The long non-coding RNA CASC15(CASC15)is considered as a tumor-related lncRNA involved in regulating biological processes such as proliferation,invasion and migration of a variety of tumor cells.However,the role of CASC15 in intracellular lipid metabolism remains unclear.The sterol-regulatory element binding proteins 1(SREBP1)is a key transcription factor that regulates lipid metabolism in cells,and its member SREBP1a mainly regulates the expression of key enzyme genes in lipid synthesis.In this paper,we investigated the effects of CASC15 on the expression and localization of lipid regulator SREBP1a in human liver cells through molecular biology and cell function experiments.The results showed that in liver cells,the mRNA and total protein levels of intracellular SREBP1a remained unchanged after overexpression of CASC15(P<0.001),while the precursor protein levels increased(P<0.05)with enhanced translocation into the nucleus;However,the levels of fatty acid synthesis-related products free fatty acids(P<0.001)and triglycerides(P<0.001)regulated by SREBP1a showed a down-regulation trend.This paper reveals a possible mechanism by which CASC15 regulates lipid metabolism in liver cells,hoping to provide new ideas for the treatment and research of diseases related to lipid metabolism disorders.