MicroRNA hsa-miR-138 Inhibits Adipogenic Differentiation of Human Adipose Tissue-Derived Mesenchymal Stem Cells Through Adenovirus EID-1

Abstract

A better understanding of the molecular mechanisms underlying the differentiation of human adipose tissue-derived mesenchymal stem cells (hAD-MSCs) could provide new insights into the pathogenesis of a number of diseases, such as obesity and diabetes, and broaden the spectrum of potential hAD-MSCs-based cell therapy. In this study, we reported that a human microRNA, hsa-miR-138, could inhibit the adipogenic differentiation of hAD-MSCs. Our results showed that miR-138 was significantly down-regulated during adipogenic differentiation. Overexpression of miR-138 in hAD-MSCs could effectively reduce lipid droplets accumulation, inhibit expression of key adipogenic transcription factors cytidine-cytidine-adenosine-adenosine-thymidine (CCAAT) enhancer binding protein alpha and peroxisome proliferator-activated receptor gamma 2 as well as several other adipogenic marker genes, such as fatty acid binding protein 4 and lipoprotein lipase. Further studies showed that the expression of adenovirus early region 1-A-like inhibitor of differentiation 1 (EID-1), a nuclear receptor coregulator, was inversely correlated with that of miR-138 when hAD-MSCs were differentiated into adipocytes. Knockdown of EID-1 by RNA interference inhibited adipocyte differentiation of hAD-MSCs. In addition, luciferase reporter assays demonstrated that miR-138 directly targeted the 3' untranslated region of EID-1, implying that the negative role of miR-138 in the adipocyte differentiation of hAD-MSCs is at least partially mediated via repressing EID-1. Taken together, this study shows that miR-138 plays a negative role in adipogenic differentiation and sheds light on the role of miRNAs during differentiation of hAD-MSCs toward adipocytes.

MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo

“…Recently, miR-138 was reported as a negative regulator of adipocyte differentiation of human adipose tissue-derived MSCs (28). These data, together with our findings, suggest a general role of miR-138 in the inhibition of hMSC differentiation and maintenance of the undifferentiated state of MSC.…”

MECHANISMS IN ENDOCRINOLOGY: Micro-RNAs: targets for enhancing osteoblast differentiation and bone formation

“…miR-138 was highly expressed in undifferentiated MSCs and down-regulated upon differentiation to osteoblastic, adipogenic and chondrogenic lineages. Based on its expression profile and functional inhibition of osteogenesis and adipogenesis (77,98), it is thus possible that miR-138 maintains MSCs in undifferentiated stage. Similarly, miR-335 down-regulation was shown to be critical for MSC differentiation, and over-expression of miR-335 inhibited both osteoblastic and adipogenic differentiation of MSCs (99).…”

let-7Enhances Osteogenesis and Bone Formation While Repressing Adipogenesis of Human Stromal/Mesenchymal Stem Cells by Regulating HMGA2

“…Emerging evidence suggests that miRNAs are involved in regulating differentiation and cell fate decisions [8]. Lots of miRNAs, including miR-143, miR-24, miR-31, miR-30c, miR-642a-3p, miR-141/200a, miR-135, miR-378, miR-196a, miR-27a, miR-26a, miR-125b, miR-133, miR-29b, miR-2861, miR-3960, miR-335-5p, miR-138, and miR-130, have been identified that are involved in the differentiation of adipocytes or osteoblasts [9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Recently, several miRNAs have also been identified to be responsible for the balance of adipogenesis and osteogenesis.…”