Altered microRNA expression profiles in large offspring syndrome and Beckwith-Wiedemann syndrome
| Autor: | Darren E. Hagen, Whitney M Frederic, Yahan Li, Mohammad Reza Bakhtiarizadeh, Tieming Ji, Emily M Traxler, Jennifer M. Kalish, Rocío Melissa Rivera |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Cancer Research Small RNA Beckwith-Wiedemann Syndrome Reproductive Techniques Assisted Beckwith–Wiedemann syndrome Cattle Diseases Down-Regulation YAP1 Reproductive technology Biology 03 medical and health sciences Genomic Imprinting 0302 clinical medicine Gene expression microRNA medicine Animals Humans Gene Regulatory Networks DLK1-DIO3 imprinted miRNA cluster Molecular Biology Gene Hippo signalling pathway Genetics bovine foetus assisted reproductive technologies DNA methylation Sequence Analysis RNA Gene Expression Profiling medicine.disease MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis large offspring syndrome Cattle Female Research Paper |
| Zdroj: | Epigenetics |
| ISSN: | 1559-2308 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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