Physiology and Pharmacology
Physiol Pharmacol
Medical Sciences
http://ppj.phypha.ir
32
journal32
24765236
24765244
10.61186/phypha
(previous ISSN: 17350581)
en
jalali
1399
9
1
gregorian
2020
12
1
24
4
online
1
fulltext
en
Network-based analysis reveals the potential involvement of proteasome subunit alpha-2 in tetralogy of Fallot
Cardiovascular Physiology/Pharmacology
Cardiovascular Physiology/Pharmacology
Experimental research article
Experimental research article
<div style="text-align: justify;"><strong>Introduction: </strong>Tetralogy of Fallot (TOF) is the most common cyanotic form of congenital heart defects. However, there is no effective therapeutic approach and current therapies have limited curative efficacy. Moreover, the exact etiology of TOF has remained largely unknown. Improved understanding of molecular mechanisms can give an insight into TOF pathogenesis and development of therapeutic approaches. <strong>Methods: </strong>Here, we conducted a systematic study on the right ventricular myocardium of 24 infants (16 ToF/8 control) using weighted gene co-expression network analysis (WGCNA) to identify meaningful modules or candidate biomarkers. <strong>Results: </strong>Co-expression network analysis by WGCNA suggested that a highly preserved turquoise module with 2,493 genes and a P-value of 3×10-11 was significantly correlated to TOF. The top 5 hub genes of this module were PSMA2, MYL12A, C11ORF71, COMMD6, and CREG1. The result of turquoise module enrichment showed that the most correlation topic in biological processes and KEGG pathways were positive regulation of cardiac neural crest migration involved in outflow tract morphogenesis and positive regulation of neural crest cell differentiation. Also, we recognized 4 FDA-approved drug candidates for other indications could potentially use for the treatment of TOF patients through regulation of two hub genes of the co-expression network (PSMA2 and NDUFA4). Our findings also showed that the 13 experimentally validated microRNAs regulated the co-expression network through 5 hub genes. <strong>Conclusion:</strong> We systematically recognized co-expressed gene modules and hub genes associated with TOF progression, which offered insights into the mechanisms underlying TOF progression and some potential drugs for the treatment of TOF.</div>
Congenital Heart Defects, Tetralogy of Fallot, Systems Biology, miRNAs, Drug Repositioning.
298
313
http://ppj.phypha.ir/browse.php?a_code=A-10-324-1&slc_lang=en&sid=1
Hassan
Karami
3200319475328460029498
3200319475328460029498
No
Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran
Maryam
Moosavi
3200319475328460029499
3200319475328460029499
No
Department of Molecular Medicine, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
Afshin
Derakhshani
3200319475328460029500
3200319475328460029500
No
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Ebrahim
Miri-Moghaddam
3200319475328460029501
3200319475328460029501
No
Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran
Marlin
Touma
3200319475328460029502
3200319475328460029502
No
Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, United States
Behzad
Baradaran
3200319475328460029503
3200319475328460029503
No
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Nazila
Alizadeh
3200319475328460029504
3200319475328460029504
No
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Hossein
Mashhadi Abdolahi
3200319475328460029505
3200319475328460029505
No
Tabriz Health Services Management Research Centre, Tabriz University of Medical Sciences, Tabriz, Iran
Khalil
Hajiasgharzadeh
hajiasgharzadeh@tbzmed.ac.ir
3200319475328460029506
3200319475328460029506
Yes
Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Hossein
Safarpour
3200319475328460029507
3200319475328460029507
No
Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran