Altered microRNA expression profiles in large offspring syndrome and Beckwith-Wiedemann syndrome
The use of assisted reproductive technologies (ART) can induce a congenital overgrowth condition in humans and ruminants, namely Beckwith-Wiedemann syndrome (BWS) and large offspring syndrome (LOS), respectively. Shared phenotypes and epigenotypes have been found between BWS and LOS. We have observe...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-09-01
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| Series: | Epigenetics |
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| Online Access: | http://dx.doi.org/10.1080/15592294.2019.1615357 |
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| author | Yahan Li Darren Erich Hagen Tieming Ji Mohammad Reza Bakhtiarizadeh Whitney M. Frederic Emily M. Traxler Jennifer M. Kalish Rocío Melissa Rivera |
| author_facet | Yahan Li Darren Erich Hagen Tieming Ji Mohammad Reza Bakhtiarizadeh Whitney M. Frederic Emily M. Traxler Jennifer M. Kalish Rocío Melissa Rivera |
| author_sort | Yahan Li |
| collection | DOAJ |
| description | The use of assisted reproductive technologies (ART) can induce a congenital overgrowth condition in humans and ruminants, namely Beckwith-Wiedemann syndrome (BWS) and large offspring syndrome (LOS), respectively. Shared phenotypes and epigenotypes have been found between BWS and LOS. We have observed global misregulation of transcripts in bovine foetuses with LOS. microRNAs (miRNAs) are important post-transcriptional gene expression regulators. We hypothesize that there is miRNA misregulation in LOS and that this misregulation is shared with BWS. In this study, small RNA sequencing was conducted to investigate miRNA expression profiles in bovine and human samples. We detected 407 abundant known miRNAs and predicted 196 putative miRNAs from the bovine sequencing results and identified 505 abundant miRNAs in human tongue. Differentially expressed miRNAs (DE-miRNAs) were identified between control and LOS groups in all tissues analysed as well as between BWS and control human samples. DE-miRNAs were detected from several miRNA clusters including DLK1-DIO3 genomic imprinted cluster in LOS and BWS. DNA hypermethylation was associated with downregulation of miRNAs in the DLK1-DIO3. mRNA targets of the DE-miRNAs were predicted and signalling pathways associated with control of organ size (including the Hippo signalling pathway), cell proliferation, apoptosis, cell survival, cell cycle, and cell adhesion were found to be enriched with these genes. Yes associated protein 1 (YAP1) is the core effector of the Hippo signalling pathway, and increased level of active (non-phosphorylated) YAP1 protein was detected in skeletal muscle of LOS foetuses. Overall, our data provide evidence of miRNA misregulation in LOS and BWS. |
| first_indexed | 2024-03-11T23:06:45Z |
| format | Article |
| id | doaj.art-ac001e9389484b93a3317259e3e7acc6 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:06:45Z |
| publishDate | 2019-09-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-ac001e9389484b93a3317259e3e7acc62023-09-21T13:09:22ZengTaylor & Francis GroupEpigenetics1559-22941559-23082019-09-0114985087610.1080/15592294.2019.16153571615357Altered microRNA expression profiles in large offspring syndrome and Beckwith-Wiedemann syndromeYahan Li0Darren Erich Hagen1Tieming Ji2Mohammad Reza Bakhtiarizadeh3Whitney M. Frederic4Emily M. Traxler5Jennifer M. Kalish6Rocío Melissa Rivera7University of MissouriOklahoma State UniversityUniversity of MissouriUniversity of TehranThe Children’s Hospital of PhiladelphiaThe Children’s Hospital of PhiladelphiaThe Children’s Hospital of PhiladelphiaUniversity of MissouriThe use of assisted reproductive technologies (ART) can induce a congenital overgrowth condition in humans and ruminants, namely Beckwith-Wiedemann syndrome (BWS) and large offspring syndrome (LOS), respectively. Shared phenotypes and epigenotypes have been found between BWS and LOS. We have observed global misregulation of transcripts in bovine foetuses with LOS. microRNAs (miRNAs) are important post-transcriptional gene expression regulators. We hypothesize that there is miRNA misregulation in LOS and that this misregulation is shared with BWS. In this study, small RNA sequencing was conducted to investigate miRNA expression profiles in bovine and human samples. We detected 407 abundant known miRNAs and predicted 196 putative miRNAs from the bovine sequencing results and identified 505 abundant miRNAs in human tongue. Differentially expressed miRNAs (DE-miRNAs) were identified between control and LOS groups in all tissues analysed as well as between BWS and control human samples. DE-miRNAs were detected from several miRNA clusters including DLK1-DIO3 genomic imprinted cluster in LOS and BWS. DNA hypermethylation was associated with downregulation of miRNAs in the DLK1-DIO3. mRNA targets of the DE-miRNAs were predicted and signalling pathways associated with control of organ size (including the Hippo signalling pathway), cell proliferation, apoptosis, cell survival, cell cycle, and cell adhesion were found to be enriched with these genes. Yes associated protein 1 (YAP1) is the core effector of the Hippo signalling pathway, and increased level of active (non-phosphorylated) YAP1 protein was detected in skeletal muscle of LOS foetuses. Overall, our data provide evidence of miRNA misregulation in LOS and BWS.http://dx.doi.org/10.1080/15592294.2019.1615357micrornalarge offspring syndromebeckwith-wiedemann syndromeassisted reproductive technologiesbovine foetusdna methylationdlk1-dio3imprinted mirna clusterhippo signalling pathwayyap1 |
| spellingShingle | Yahan Li Darren Erich Hagen Tieming Ji Mohammad Reza Bakhtiarizadeh Whitney M. Frederic Emily M. Traxler Jennifer M. Kalish Rocío Melissa Rivera Altered microRNA expression profiles in large offspring syndrome and Beckwith-Wiedemann syndrome Epigenetics microrna large offspring syndrome beckwith-wiedemann syndrome assisted reproductive technologies bovine foetus dna methylation dlk1-dio3 imprinted mirna cluster hippo signalling pathway yap1 |
| title | Altered microRNA expression profiles in large offspring syndrome and Beckwith-Wiedemann syndrome |
| title_full | Altered microRNA expression profiles in large offspring syndrome and Beckwith-Wiedemann syndrome |
| title_fullStr | Altered microRNA expression profiles in large offspring syndrome and Beckwith-Wiedemann syndrome |
| title_full_unstemmed | Altered microRNA expression profiles in large offspring syndrome and Beckwith-Wiedemann syndrome |
| title_short | Altered microRNA expression profiles in large offspring syndrome and Beckwith-Wiedemann syndrome |
| title_sort | altered microrna expression profiles in large offspring syndrome and beckwith wiedemann syndrome |
| topic | microrna large offspring syndrome beckwith-wiedemann syndrome assisted reproductive technologies bovine foetus dna methylation dlk1-dio3 imprinted mirna cluster hippo signalling pathway yap1 |
| url | http://dx.doi.org/10.1080/15592294.2019.1615357 |
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