title: miR-138/miR-222 Overexpression Characterizes the miRNome of Amniotic Mesenchymal Stem Cells in Obesity.
abstract: Clinical findings and data obtained in animal models indicate that nutrient uptake and exposure to environmental agents during pregnancy may affect fetal/newborn gestational programming, thereby resulting in obesity and/or obesity-related disorders in offspring. Human amniotic mesenchymal stem cells (hA-MSCs) differentiate into adipocytes and are thus a suitable model to investigate adipocyte functions in obesity. The aim of this study was to elucidate the miRNome of hA-MSCs and its contribution to obesity in pregnancy. To this aim we used the following: (i) high-resolution small RNA sequencing to characterize the microRNA (miRNA) profiles of hA-MSCs of 13 obese (Ob-) and 7 control (Co-) pregnant women at delivery; (ii) multiple-method integrated bioinformatics to predict the metabolic pathways potentially miRNA deregulated in Ob-hA-MSCs; and (iii) microarray mRNA expression profiling to verify obese-associated mRNA alterations. In summary, 12 miRNAs were differentially expressed between Ob-hA-MSCs and Co-hA-MSCs, with a multiple-methods bioinformatic consensus on miR-138-5p and miR-222-3p, which were overexpressed in Ob-hA-MSCs versus Co-hA-MSCs. The top 20 significant pathways predicted to be deregulated through miR-138-5p and/or miR-222-3p/target interaction included fat cell differentiation and deposits, lipid/carbohydrate homeostasis, response to stress, metabolic syndrome, heart disease, and ischemia. In conclusion, our finding of miR-138-5p/miR-222-3p overexpression in Ob-hA-MSCs, together with the transcriptomic data, suggests that these miRNAs in obese pregnancy could derange metabolic pathways previously found impaired in tissues from obese adults or in obesity-associated disorders and concur to modify gestational programming as has been demonstrated in animal models. This raises the possibility of using diet-based strategies to normalize the perinatal miRNome in obesity.
authors.affiliation: 1 CEINGE-Biotecnologie Avanzate S.C.a R.L. , Naples, Italy .|2 Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II , Naples, Italy .
authors.forename: Carmela
authors.initials: C
authors.lastname: Nardelli
authors.affiliation: 3 LabGTP (Laboratory of Genomics, Transcriptomics and Proteomics), Institute for High Performance Computing and Networking (ICAR) , National Research Council (CNR), Naples, Italy .
authors.forename: Ilaria
authors.initials: I
authors.lastname: Granata
authors.affiliation: 1 CEINGE-Biotecnologie Avanzate S.C.a R.L. , Naples, Italy .|2 Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II , Naples, Italy .
authors.forename: Laura
authors.initials: L
authors.lastname: Iaffaldano
authors.affiliation: 1 CEINGE-Biotecnologie Avanzate S.C.a R.L. , Naples, Italy .|2 Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II , Naples, Italy .
authors.forename: Valeria
authors.initials: V
authors.lastname: D'Argenio
authors.affiliation: 1 CEINGE-Biotecnologie Avanzate S.C.a R.L. , Naples, Italy .
authors.forename: Valentina
authors.initials: V
authors.lastname: Del Monaco
authors.affiliation: 4 Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Università degli Studi di Napoli Federico II , Naples, Italy .
authors.forename: Giuseppe Maria
authors.initials: GM
authors.lastname: Maruotti
authors.affiliation: 5 Institute of Genetics and Biophysics "Adriano-Buzzati Traverso ," CNR, Naples, Italy .
authors.forename: Daniela
authors.initials: D
authors.lastname: Omodei
authors.affiliation: 1 CEINGE-Biotecnologie Avanzate S.C.a R.L. , Naples, Italy .|2 Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II , Naples, Italy .
authors.forename: Luigi
authors.initials: L
authors.lastname: Del Vecchio
authors.affiliation: 4 Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Università degli Studi di Napoli Federico II , Naples, Italy .
authors.forename: Pasquale
authors.initials: P
authors.lastname: Martinelli
authors.affiliation: 1 CEINGE-Biotecnologie Avanzate S.C.a R.L. , Naples, Italy .|2 Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II , Naples, Italy .
authors.forename: Francesco
authors.initials: F
authors.lastname: Salvatore
authors.affiliation: 3 LabGTP (Laboratory of Genomics, Transcriptomics and Proteomics), Institute for High Performance Computing and Networking (ICAR) , National Research Council (CNR), Naples, Italy .
authors.forename: Mario Rosario
authors.initials: MR
authors.lastname: Guarracino
authors.affiliation: 1 CEINGE-Biotecnologie Avanzate S.C.a R.L. , Naples, Italy .
authors.forename: Lucia
authors.initials: L
authors.lastname: Sacchetti
authors.affiliation: 1 CEINGE-Biotecnologie Avanzate S.C.a R.L. , Naples, Italy .|2 Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II , Naples, Italy .
authors.forename: Lucio
authors.initials: L
authors.lastname: Pastore
mesh_terms: D000328:Adult; D000650:Amnion / Q000473:pathology*; D001483:Base Sequence; D016022:Case-Control Studies; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015723:Gene Library; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D009765:Obesity / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results
chemical_list: D035683:MicroRNAs; C546110:MIRN138 microRNA, human; C525710:MIR222, human
keywords: RNA-sequencing; human amniotic mesenchymal stem cells; miRNome; obesity; pregnancy