Long Non-coding RNA 332443 Inhibits Preadipocyte Differentiation by Targeting Runx1 and p38-MAPK and ERK1/2-MAPK Signaling Pathways.
Long Non-coding RNA 332443 Inhibits Preadipocyte Differentiation by Targeting Runx1 and p38-MAPK and ERK1/2-MAPK Signaling Pathways.
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长非编码 RNA 332443 通过靶向 Runx1 和 p38-MAPK 和 ERK1/2-MAPK 信号通路抑制前脂肪细胞分化
DOI：
10.3389/fcell.2021.663959
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zhou HD
中科院分区：
文献类型：
--
作者：
Xiao F;Tang CY;Tang HN;Wu HX;Hu N;Li L;Zhou HD
长非编码RNAs(Long Non-Coding RNAs，LncRNAs)已成为病理生理过程中不可或缺的调节因子，但其在脂肪组织发育中的具体作用和机制仍不清楚。在此，通过基因芯片分析、共表达和组织特异性分析发现，禁食72小时后，LNC-FR332443的表达显著降低，RUNX1的表达也显著降低。UCSC数据库和EnSembl数据库表明，LNC-FR332443是RUNX1的反义lncRNA。LNC-FR332443和RUNX1在脂肪组织中高度丰富，在成脂分化过程中表达下调。脂肪组织特异性敲除LNC-FR332443可增加体内脂肪质量，在3T3-L1前脂肪细胞中特异性敲除LNC-FR332443可促进成脂分化。在这个过程中，当LNC-FR332443在脂肪细胞或3T3-L1前脂肪细胞中下调时，RUNX1的表达减少，反之亦然，当LNC-FR332443上调时，RUNX1的表达增加。然而，过表达RUNX1显著降低了脂肪细胞标志基因PPARγ、C/EBPα和FABP4的表达，而对LNC-FR332443的表达没有影响。机制上，LNC-FR332443通过抑制MAPK-p38的磷酸化和MAPK-ERK1/2的表达，正向调节小鼠脂肪细胞RUNX1的表达，抑制脂肪细胞的分化。因此，本研究表明LNC-FR332443具有抑制脂肪生成的作用，可能成为防治肥胖的药物靶点。
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 Lnc-FR332443 expression was dramatically decreased, as well as the expression of Runx1. The UCSC database and Ensembl database indicated that Lnc-FR332443 is the antisense lncRNA of Runx1. Lnc-FR332443 and Runx1 are highly enriched in adipose tissue and downregulated during adipogenic differentiation. Adipose tissue-specific knockdown of Lnc-FR332443 increased fat mass in vivo, and specific knockdown of Lnc-FR332443 in 3T3-L1 preadipocytes promoted adipogenic differentiation. In this process, Runx1 expression was decreased when Lnc-FR332443 was downregulated in adipocytes or 3T3-L1 preadipocytes, and vice versa, when Lnc-FR332443 was upregulated, the expression of Runx1 was increased. However, overexpression of Runx1 decreased the expression of the adipocyte cell marker genes PPARγ, C/EBPα and FABP4 significantly, while not affected the expression of Lnc-FR332443. Mechanistically, Lnc-FR332443 positively regulates Runx1 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 Lnc-FR332443 inhibits adipogenesis and which might be a drug target for the prevention and treatment of obesity.
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脂肪组织转录组的从头重建揭示了棕色脂肪细胞发育的长无编码RNA调节剂。
影响因子：
29
作者：
Alvarez-Dominguez JR;Bai Z;Xu D;Yuan B;Lo KA;Yoon MJ;Lim YC;Knoll M;Slavov N;Chen S;Peng C;Lodish HF;Sun L
通讯作者：
Sun L
DOI：
10.1038/nrm.2017.104
发表时间：
2018-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Ransohoff JD;Wei Y;Khavari PA
通讯作者：
Khavari PA
影响因子：
5.6
作者：
Fayyad, Abeer Maher;Khan, Amir Ali;Khattak, Muhammad Nasir Khan
通讯作者：
Khattak, Muhammad Nasir Khan
影响因子：
11.2
作者：
Kilbey A;Terry A;Jenkins A;Borland G;Zhang Q;Wakelam MJ;Cameron ER;Neil JC
通讯作者：
Neil JC
影响因子：
5.6
作者：
Leblanc, Kimberly T.;Walcott, Marie E.;Gaur, Tripti;O'Connell, Shannon L.;Basil, Kirti;Tadiri, Christina P.;Mason-Savas, April;Silva, Jason A.;van Wijnen, Andre J.;Stein, Janet L.;Stein, Gary S.;Ayers, David C.;Lian, Jane B.;Fanning, Paul J.
通讯作者：
Fanning, Paul J.