Long noncoding RNA LYPLAL1-AS1 regulates adipogenic differentiation of human mesenchymal stem cells by targeting desmoplakin and inhibiting the Wnt/β-catenin pathway

Autor: Yanlei Yang, Junfen Fan, Haoying Xu, Linyuan Fan, Luchan Deng, Jing Li, Di Li, Hongling Li, Fengchun Zhang, Robert Chunhua Zhao
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Cell Death Discovery, Vol 7, Iss 1, Pp 1-16 (2021)
Druh dokumentu: article
ISSN: 2058-7716
DOI: 10.1038/s41420-021-00500-5
Popis: Abstract Long noncoding RNAs are crucial factors for modulating adipogenic differentiation, but only a few have been identified in humans. In the current study, we identified a previously unknown human long noncoding RNA, LYPLAL1-antisense RNA1 (LYPLAL1-AS1), which was dramatically upregulated during the adipogenic differentiation of human adipose-derived mesenchymal stem cells (hAMSCs). Based on 5′ and 3′ rapid amplification of cDNA ends assays, full-length LYPLAL1-AS1 was 523 nt. Knockdown of LYPLAL1-AS1 decreased the adipogenic differentiation of hAMSCs, whereas overexpression of LYPLAL1-AS1 enhanced this process. Desmoplakin (DSP) was identified as a direct target of LYPLAL1-AS1. Knockdown of DSP enhanced adipogenic differentiation and rescued the LYPLAL1-AS1 depletion-induced defect in adipogenic differentiation of hAMSCs. Further experiments showed that LYPLAL1-AS1 modulated DSP protein stability possibly via proteasome degradation, and the Wnt/β-catenin pathway was inhibited during adipogenic differentiation regulated by the LYPLAL1-AS1/DSP complex. Together, our work provides a new mechanism by which long noncoding RNA regulates adipogenic differentiation of human MSCs and suggests that LYPLAL1-AS1 may serve as a novel therapeutic target for preventing and combating diseases related to abnormal adipogenesis, such as obesity.
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