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

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

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2021.663959

DOI=10.3389/fcell.2021.663959

ISSN=2296-634X

ABSTRACT=<p>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 <italic>Lnc-FR332443</italic> expression was dramatically decreased, as well as the expression of <italic>Runx1</italic>. The UCSC database and Ensembl database indicated that <italic>Lnc-FR332443</italic> is the antisense lncRNA of <italic>Runx1</italic>. <italic>Lnc-FR332443</italic> and <italic>Runx1</italic> are highly enriched in adipose tissue and downregulated during adipogenic differentiation. Adipose tissue-specific knockdown of <italic>Lnc-FR332443</italic> increased fat mass <italic>in vivo</italic>, and specific knockdown of <italic>Lnc-FR332443</italic> in 3T3-L1 preadipocytes promoted adipogenic differentiation. In this process, <italic>Runx1</italic> expression was decreased when <italic>Lnc-FR332443</italic> was downregulated in adipocytes or 3T3-L1 preadipocytes, and vice versa, when <italic>Lnc-FR332443</italic> was upregulated, the expression of <italic>Runx1</italic> was increased. However, overexpression of <italic>Runx1</italic> decreased the expression of the adipocyte cell marker genes <italic>PPAR</italic>γ, <italic>C/EBP</italic>α and <italic>FABP4</italic> significantly, while not affected the expression of <italic>Lnc-FR332443.</italic> Mechanistically, <italic>Lnc-FR332443</italic> positively regulates <italic>Runx1</italic> 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 <italic>Lnc-FR332443</italic> inhibits adipogenesis and which might be a drug target for the prevention and treatment of obesity.</p>