PMID- 33946378 OWN - NLM STAT- MEDLINE DCOM- 20211021 LR - 20211021 IS - 2073-4409 (Electronic) IS - 2073-4409 (Linking) VI - 10 IP - 5 DP - 2021 Apr 30 TI - Integrated microRNA and mRNA Expression Profiling Identifies Novel Targets and Networks Associated with Ebstein's Anomaly. LID - 10.3390/cells10051066 [doi] LID - 1066 AB - Little is known about abundance level changes of circulating microRNAs (miRNAs) and messenger RNAs (mRNA) in patients with Ebstein's anomaly (EA). Here, we performed an integrated analysis to identify the differentially abundant miRNAs and mRNA targets and to identify the potential therapeutic targets that might be involved in the mechanisms underlying EA. A large panel of human miRNA and mRNA microarrays were conducted to determine the genome-wide expression profiles in the blood of 16 EA patients and 16 age and gender-matched healthy control volunteers (HVs). Differential abundance level of single miRNA and mRNA was validated by Real-Time quantitative PCR (RT-qPCR). Enrichment analyses of altered miRNA and mRNA abundance levels were identified using bioinformatics tools. Altered miRNA and mRNA abundance levels were observed between EA patients and HVs. Among the deregulated miRNAs and mRNAs, 76 miRNAs (49 lower abundance and 27 higher abundance, fold-change of >/=2) and 29 mRNAs (25 higher abundance and 4 lower abundance, fold-change of >/=1.5) were identified in EA patients compared to HVs. Bioinformatics analysis identified 37 pairs of putative miRNA-mRNA interactions. The majority of the correlations were detected between the lower abundance level of miRNA and higher abundance level of mRNA, except for let-7b-5p, which showed a higher abundance level and their target gene, SCRN3, showed a lower abundance level. Pathway enrichment analysis of the deregulated mRNAs identified 35 significant pathways that are mostly involved in signal transduction and cellular interaction pathways. Our findings provide new insights into a potential molecular biomarker(s) for the EA that may guide the development of novel targeting therapies. FAU - Abu-Halima, Masood AU - Abu-Halima M AUID- ORCID: 0000-0001-9048-4958 AD - Institute of Human Genetics, Saarland University, 66421 Homburg/Saar, Germany. AD - Department of Pediatric Cardiology, Saarland University Medical Center, 66421 Homburg/Saar, Germany. FAU - Wagner, Viktoria AU - Wagner V AUID- ORCID: 0000-0002-1957-0658 AD - Institute of Human Genetics, Saarland University, 66421 Homburg/Saar, Germany. AD - Center for Clinical Bioinformatics, Saarland University, 66123 Saarbrucken, Germany. FAU - Becker, Lea Simone AU - Becker LS AD - Institute of Human Genetics, Saarland University, 66421 Homburg/Saar, Germany. FAU - Ayesh, Basim M AU - Ayesh BM AUID- ORCID: 0000-0001-5905-9611 AD - Department of Laboratory Medical Sciences, Alaqsa University, Gaza 4051, Palestine. FAU - Abd El-Rahman, Mohammed AU - Abd El-Rahman M AD - Department of Pediatric Cardiology, Saarland University Medical Center, 66421 Homburg/Saar, Germany. FAU - Fischer, Ulrike AU - Fischer U AUID- ORCID: 0000-0002-7808-9565 AD - Institute of Human Genetics, Saarland University, 66421 Homburg/Saar, Germany. FAU - Meese, Eckart AU - Meese E AD - Institute of Human Genetics, Saarland University, 66421 Homburg/Saar, Germany. FAU - Abdul-Khaliq, Hashim AU - Abdul-Khaliq H AD - Department of Pediatric Cardiology, Saarland University Medical Center, 66421 Homburg/Saar, Germany. LA - eng GR - 2016/Hedwig-Stalter-Stiftung/ GR - [Nr. 01GI0601 (2014)]/Competence Network for Congenital Heart Defects/ GR - [Nr. 81X2800112 (2015)]/German Centre for Cardiovascular Research (DZHK)/ GR - 2021/Fordergemeinschaft Kinderherzen/Deutsche Herzstiftung/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210430 PL - Switzerland TA - Cells JT - Cells JID - 101600052 RN - 0 (MicroRNAs) RN - 0 (RNA, Messenger) SB - IM MH - Adolescent MH - Adult MH - Ebstein Anomaly/*genetics/metabolism MH - Female MH - *Gene Regulatory Networks MH - Humans MH - Male MH - MicroRNAs/*genetics/metabolism MH - RNA, Messenger/*genetics/metabolism MH - Transcriptome PMC - PMC8146150 OTO - NOTNLM OT - Ebstein's anomaly OT - congenital heart defect OT - integration analysis OT - mRNA OT - microRNA COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2021/05/06 06:00 MHDA- 2023/02/25 06:00 PMCR- 2021/04/30 CRDT- 2021/05/05 01:01 PHST- 2021/03/24 00:00 [received] PHST- 2021/04/27 00:00 [revised] PHST- 2021/04/28 00:00 [accepted] PHST- 2021/05/05 01:01 [entrez] PHST- 2021/05/06 06:00 [pubmed] PHST- 2023/02/25 06:00 [medline] PHST- 2021/04/30 00:00 [pmc-release] AID - cells10051066 [pii] AID - cells-10-01066 [pii] AID - 10.3390/cells10051066 [doi] PST - epublish SO - Cells. 2021 Apr 30;10(5):1066. doi: 10.3390/cells10051066.