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长链非编码RNA 332443通过靶向Runx1以及p38-MAPK和ERK1/2-MAPK信号通路抑制前脂肪细胞分化。

Long Non-coding RNA 332443 Inhibits Preadipocyte Differentiation by Targeting Runx1 and p38-MAPK and ERK1/2-MAPK Signaling Pathways.

作者信息

Xiao Fen, Tang Chen-Yi, Tang Hao-Neng, Wu Hui-Xuan, Hu Nan, Li Long, Zhou Hou-De

机构信息

National Clinical Research Center for Metabolic Diseases, Hunan Provincial Key Laboratory of Metabolic Bone Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.

出版信息

Front Cell Dev Biol. 2021 Jun 8;9:663959. doi: 10.3389/fcell.2021.663959. eCollection 2021.

Abstract

Long non-coding RNAs (lncRNAs) have emerged as integral regulators of pathophysiological processes, but their specific roles and mechanisms in adipose tissue development remain largely unknown. Here, through microarray analysis, co-expression, and tissue specific analysis of adipocyte tissues after fasting for 72 h, we found that expression was dramatically decreased, as well as the expression of . The UCSC database and Ensembl database indicated that is the antisense lncRNA of . and are highly enriched in adipose tissue and downregulated during adipogenic differentiation. Adipose tissue-specific knockdown of increased fat mass , and specific knockdown of in 3T3-L1 preadipocytes promoted adipogenic differentiation. In this process, expression was decreased when was downregulated in adipocytes or 3T3-L1 preadipocytes, and vice versa, when was upregulated, the expression of was increased. However, overexpression of decreased the expression of the adipocyte cell marker genes γ, α and significantly, while not affected the expression of Mechanistically, positively regulates expression in mouse adipocytes and suppresses adipocyte differentiation by attenuating the phosphorylation of MAPK-p38 and MAPK-ERK1/2 expression. Thus, this study indicated that inhibits adipogenesis and which might be a drug target for the prevention and treatment of obesity.

摘要

长链非编码RNA(lncRNAs)已成为病理生理过程的重要调节因子,但其在脂肪组织发育中的具体作用和机制仍 largely未知。在这里,通过对禁食72小时后的脂肪细胞组织进行微阵列分析、共表达分析和组织特异性分析,我们发现 表达显著降低,以及 的表达也降低。UCSC数据库和Ensembl数据库表明 是 的反义lncRNA。 和 在脂肪组织中高度富集,并在脂肪生成分化过程中下调。脂肪组织特异性敲低 增加了脂肪量 ,在3T3-L1前脂肪细胞中特异性敲低 促进了脂肪生成分化。在这个过程中,当 在脂肪细胞或3T3-L1前脂肪细胞中下调时, 表达降低,反之,当 上调时, 的表达增加。然而, 的过表达显著降低了脂肪细胞标记基因γ、α和 的表达,而不影响 的表达。机制上, 在小鼠脂肪细胞中正向调节 表达,并通过减弱MAPK-p38的磷酸化和MAPK-ERK1/2的表达来抑制脂肪细胞分化。因此,本研究表明 抑制脂肪生成,这可能是预防和治疗肥胖症的药物靶点。

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