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长链非编码 RNA LIPE-AS1 在脂肪生成中的作用。

Role of lncRNA LIPE-AS1 in adipogenesis.

机构信息

Department of Molecular Imaging and Therapy, Beckman Research Institute of City of Hope, Duarte, CA, USA.

Irell and Manella Graduate School of Biological Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA.

出版信息

Adipocyte. 2022 Dec;11(1):11-27. doi: 10.1080/21623945.2021.2013415.

Abstract

Recent studies have identified long non-coding RNAs (lncRNAs) as potential regulators of adipogenesis. In this study, we have characterized a lncRNA, LIPE-AS1, that spans genes to in man with conservation of genomic organization and tissue expression between mouse and man. Tissue-specific expression of isoforms of the murine lncRNA were found in liver and adipose tissue, one of which, designated mLas-V3, overlapped the gene encoding hormone-sensitive lipase in both mouse and man suggesting that it may have a functional role in adipose tissue. Knock down of expression of mLas-V3 using anti-sense oligos (ASOs) led to a significant decrease in the differentiation of the OP9 pre-adipocyte cell line through the down regulation of the major adipogenic transcription factors and . Knock down of mLas-V3 induced apoptosis during the differentiation of OP9 cells as shown by expression of active caspase-3, a change in the localization of LIP/LAP isoforms of C/EBPβ, and expression of the cellular stress induced factors CHOP, p53, PUMA, and NOXA. We conclude that mLas-V3 may play a role in protecting against stress associated with adipogenesis, and its absence leads to apoptosis.

摘要

最近的研究已经确定了长非编码 RNA(lncRNA)是脂肪生成的潜在调节剂。在这项研究中,我们对一个跨越人类基因 到 的 lncRNA 进行了特征描述,其基因组组织和组织表达在小鼠和人类之间具有保守性。小鼠 lncRNA 的同工型在肝脏和脂肪组织中具有组织特异性表达,其中一个同工型,命名为 mLas-V3,在小鼠和人类中与编码激素敏感脂肪酶的基因重叠,这表明它可能在脂肪组织中具有功能作用。使用反义寡核苷酸 (ASO) 敲低 mLas-V3 的表达会导致 OP9 前脂肪细胞系的分化显著减少,这是通过下调主要的脂肪生成转录因子 和 实现的。敲低 mLas-V3 会诱导 OP9 细胞分化过程中的细胞凋亡,这表现为活性半胱天冬酶-3 的表达、C/EBPβ 的 LIP/LAP 同工型的定位变化以及细胞应激诱导因子 CHOP、p53、PUMA 和 NOXA 的表达。我们得出结论,mLas-V3 可能在保护脂肪生成相关应激方面发挥作用,其缺失会导致细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b8dd/8726699/2eb9f1653b25/KADI_A_2013415_F0001_OC.jpg

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