microRNA-27a-3p but Not -5p Is a Crucial Mediator of Human Adipogenesis

MicroRNAs (miRNAs), a class of small, non-coding RNA molecules, play an important role in the posttranscriptional regulation of gene expression, thereby influencing important cellular functions. In adipocytes, miRNAs show import regulatory features and are described to influence differentiation as w...

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Autores principales:	Hang Wu, Taner Pula, Daniel Tews, Ez-Zoubir Amri, Klaus-Michael Debatin, Martin Wabitsch, Pamela Fischer-Posovszky, Julian Roos
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	microRNA-27a adipocytes adipogenesis PPARγ LPL Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/64fd73d8552c41d4896d5fdb68c64986
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spelling	oai:doaj.org-article:64fd73d8552c41d4896d5fdb68c649862021-11-25T17:12:51ZmicroRNA-27a-3p but Not -5p Is a Crucial Mediator of Human Adipogenesis10.3390/cells101132052073-4409https://doaj.org/article/64fd73d8552c41d4896d5fdb68c649862021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3205https://doaj.org/toc/2073-4409MicroRNAs (miRNAs), a class of small, non-coding RNA molecules, play an important role in the posttranscriptional regulation of gene expression, thereby influencing important cellular functions. In adipocytes, miRNAs show import regulatory features and are described to influence differentiation as well as metabolic, endocrine, and inflammatory functions. We previously identified miR-27a being upregulated under inflammatory conditions in human adipocytes and aimed to elucidate its function in adipocyte biology. Both strands of miR-27a, miR-27a-3p and -5p, were downregulated during the adipogenic differentiation of Simpson–Golabi–Behmel syndrome (SGBS) cells, human multipotent adipose-derived stem cells (hMADS), and human primary adipose-derived stromal cells (hASCs). Using miRNA-mimic transfection, we observed that miR-27a-3p is a crucial regulator of adipogenesis, while miR-27a-5p did not alter the differentiation capacity in SGBS cells. In silico screening predicted lipoprotein lipase (LPL) and peroxisome proliferator activated receptor γ (PPARγ) as potential targets of miR-27a-3p. The downregulation of both genes was verified in vitro, and the interaction of miR-27-3p with target sites in the 3′ UTRs of both genes was confirmed via a miRNA-reporter-gene assay. Here, the knockdown of LPL did not interfere with adipogenic differentiation, while PPARγ knockdown decreased adipogenesis significantly, suggesting that miR-27-3p exerts its inhibitory effect on adipogenesis by repressing PPARγ. Taken together, we identified and validated a crucial role for miR-27a-3p in human adipogenesis played by targeting the essential adipogenic transcription factor PPARγ. Though we confirmed LPL as an additional target of miR-27a-3p, it does not appear to be involved in regulating human adipogenesis. Thereby, our findings call the conclusions drawn from previous studies, which identified LPL as a crucial regulator for murine and human adipogenesis, into question.Hang WuTaner PulaDaniel TewsEz-Zoubir AmriKlaus-Michael DebatinMartin WabitschPamela Fischer-PosovszkyJulian RoosMDPI AGarticlemicroRNA-27aadipocytesadipogenesisPPARγLPLBiology (General)QH301-705.5ENCells, Vol 10, Iss 3205, p 3205 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	microRNA-27a adipocytes adipogenesis PPARγ LPL Biology (General) QH301-705.5
spellingShingle	microRNA-27a adipocytes adipogenesis PPARγ LPL Biology (General) QH301-705.5 Hang Wu Taner Pula Daniel Tews Ez-Zoubir Amri Klaus-Michael Debatin Martin Wabitsch Pamela Fischer-Posovszky Julian Roos microRNA-27a-3p but Not -5p Is a Crucial Mediator of Human Adipogenesis
description	MicroRNAs (miRNAs), a class of small, non-coding RNA molecules, play an important role in the posttranscriptional regulation of gene expression, thereby influencing important cellular functions. In adipocytes, miRNAs show import regulatory features and are described to influence differentiation as well as metabolic, endocrine, and inflammatory functions. We previously identified miR-27a being upregulated under inflammatory conditions in human adipocytes and aimed to elucidate its function in adipocyte biology. Both strands of miR-27a, miR-27a-3p and -5p, were downregulated during the adipogenic differentiation of Simpson–Golabi–Behmel syndrome (SGBS) cells, human multipotent adipose-derived stem cells (hMADS), and human primary adipose-derived stromal cells (hASCs). Using miRNA-mimic transfection, we observed that miR-27a-3p is a crucial regulator of adipogenesis, while miR-27a-5p did not alter the differentiation capacity in SGBS cells. In silico screening predicted lipoprotein lipase (LPL) and peroxisome proliferator activated receptor γ (PPARγ) as potential targets of miR-27a-3p. The downregulation of both genes was verified in vitro, and the interaction of miR-27-3p with target sites in the 3′ UTRs of both genes was confirmed via a miRNA-reporter-gene assay. Here, the knockdown of LPL did not interfere with adipogenic differentiation, while PPARγ knockdown decreased adipogenesis significantly, suggesting that miR-27-3p exerts its inhibitory effect on adipogenesis by repressing PPARγ. Taken together, we identified and validated a crucial role for miR-27a-3p in human adipogenesis played by targeting the essential adipogenic transcription factor PPARγ. Though we confirmed LPL as an additional target of miR-27a-3p, it does not appear to be involved in regulating human adipogenesis. Thereby, our findings call the conclusions drawn from previous studies, which identified LPL as a crucial regulator for murine and human adipogenesis, into question.
format	article
author	Hang Wu Taner Pula Daniel Tews Ez-Zoubir Amri Klaus-Michael Debatin Martin Wabitsch Pamela Fischer-Posovszky Julian Roos
author_facet	Hang Wu Taner Pula Daniel Tews Ez-Zoubir Amri Klaus-Michael Debatin Martin Wabitsch Pamela Fischer-Posovszky Julian Roos
author_sort	Hang Wu
title	microRNA-27a-3p but Not -5p Is a Crucial Mediator of Human Adipogenesis
title_short	microRNA-27a-3p but Not -5p Is a Crucial Mediator of Human Adipogenesis
title_full	microRNA-27a-3p but Not -5p Is a Crucial Mediator of Human Adipogenesis
title_fullStr	microRNA-27a-3p but Not -5p Is a Crucial Mediator of Human Adipogenesis
title_full_unstemmed	microRNA-27a-3p but Not -5p Is a Crucial Mediator of Human Adipogenesis
title_sort	microrna-27a-3p but not -5p is a crucial mediator of human adipogenesis
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/64fd73d8552c41d4896d5fdb68c64986
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microRNA-27a-3p but Not -5p Is a Crucial Mediator of Human Adipogenesis

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