Angela Caponnetto1, Rosalia Battaglia1, Carmen Ferrara1, Maria Elena Vento2, Placido Borzì2, Marianna Paradiso2, Paolo Scollo2, Michele Purrello1, Salvatore Longobardi3, Thomas D'Hooghe4, Domenico Valerio5, Cinzia Di Pietro6. 1. Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics "Giovanni Sichel, University of Catania, 95123, Catania, Italy. 2. IVF Unit, Cannizzaro Hospital, Catania, Italy. 3. Global Clinical Development, Merck Serono SpA, Rome, Italy. 4. Global Medical Affairs Fertility, R&D Healthcare, the Healthcare Business of Merck KGaA, Frankfurter Str. 250, 64293, Darmstadt, Germany. 5. Institute of Genetic Research (IRG), 80143, Naples, Italy. 6. Department of Biomedical and Biotechnological Sciences, Section of Biology and Genetics "Giovanni Sichel, University of Catania, 95123, Catania, Italy. dipietro@unict.it.
Abstract
PURPOSE: Long non-coding RNAs (lncRNAs) control gene expression at multiple levels. By interacting with microRNAs (miRNAs), they regulate their mRNA targets creating dynamic regulatory networks involved in different cellular processes. Their role in follicle development and oocyte maturation has recently emerged. lncRNA deregulation has been found associated with different pathological conditions. In this study, we identified differentially expressed lncRNAs in cumulus cells (CCs) isolated from MII oocytes of advanced maternal age women and proposed ceRNA-networks involved in signaling pathways crucial in ovarian folliculogenesis and female germ cell maturation. METHODS: We performed a high-throughput analysis of the expression profile of 68 lncRNAs from CCs of aged and young women by using NanoString technology. By miRNet, TarPmiR, miRTarBase, OKdb, and KEGG we predicted some ceRNA-networks involving the differentially expressed (DE) lncRNAs, miRNA interactors, and their mRNA target genes. RESULTS: We identified 28 lncRNAs down-regulated in CC samples from aged women. The analysis revealed that the miRNAs binding 11 of the DE lncRNAs and their mRNA targets are included in ceRNA-networks involved in the regulation of the PI3K-Akt, FOXO, and p53 signaling pathways. CONCLUSION: We proposed that the lncRNA down-regulation in CCs from aged women could influence the expression of genes encoding proteins deregulated in reproductive aging. A better understanding of the interplay of lncRNA-miRNA-mRNA networks in human CCs could increase our knowledge about the mechanisms of regulation of gene expression involved in aging, lead to the development of novel therapeutics, and improve reproductive outcomes in aged women.
PURPOSE: Long non-coding RNAs (lncRNAs) control gene expression at multiple levels. By interacting with microRNAs (miRNAs), they regulate their mRNA targets creating dynamic regulatory networks involved in different cellular processes. Their role in follicle development and oocyte maturation has recently emerged. lncRNA deregulation has been found associated with different pathological conditions. In this study, we identified differentially expressed lncRNAs in cumulus cells (CCs) isolated from MII oocytes of advanced maternal age women and proposed ceRNA-networks involved in signaling pathways crucial in ovarian folliculogenesis and female germ cell maturation. METHODS: We performed a high-throughput analysis of the expression profile of 68 lncRNAs from CCs of aged and young women by using NanoString technology. By miRNet, TarPmiR, miRTarBase, OKdb, and KEGG we predicted some ceRNA-networks involving the differentially expressed (DE) lncRNAs, miRNA interactors, and their mRNA target genes. RESULTS: We identified 28 lncRNAs down-regulated in CC samples from aged women. The analysis revealed that the miRNAs binding 11 of the DE lncRNAs and their mRNA targets are included in ceRNA-networks involved in the regulation of the PI3K-Akt, FOXO, and p53 signaling pathways. CONCLUSION: We proposed that the lncRNA down-regulation in CCs from aged women could influence the expression of genes encoding proteins deregulated in reproductive aging. A better understanding of the interplay of lncRNA-miRNA-mRNA networks in human CCs could increase our knowledge about the mechanisms of regulation of gene expression involved in aging, lead to the development of novel therapeutics, and improve reproductive outcomes in aged women.
Authors: Susanna McReynolds; Monika Dzieciatkowska; Blair R McCallie; Shane D Mitchell; John Stevens; Kirk Hansen; William B Schoolcraft; Mandy G Katz-Jaffe Journal: Fertil Steril Date: 2012-09-08 Impact factor: 7.329
Authors: C Dell'Aversana; F Cuomo; S Longobardi; T D'Hooghe; F Caprio; G Franci; M Santonastaso; N Colacurci; S Barone; V Pisaturo; D Valerio; L Altucci Journal: Hum Reprod Date: 2021-04-20 Impact factor: 6.918