Sains Malaysiana 53(12)(2024): 3895-3906
http://doi.org/10.17576/jsm-2024-5312-05
Unveiling Common Pathways and Potential Drug Targets
for Ulcerative Colitis and IgG4-Related Disease through Bioinformatics Analysis
(Mendedahkan Laluan Biasa dan Sasaran Dadah Berpotensi untuk Kolitis Ulseratif dan Penyakit Berkaitan IgG4 melalui Analisis Bioinformatik)
QUAN LIAO1#, HONGJIAN
ZHANG1#, FANGYUAN ZHOU1, HUASHENG LIN2,
XIONGWEI ZHENG1, ZHIYUN WENG3, KAIYUE LI4,
ZHENG WAN1, & HENG PAN1*
1Zhongshan Hospital Xiamen
University, School of Medicine, Xiamen University, Xiamen City, 361000, Fujian,
China
2Guangdong Medical University, Dongguan City, 523000, Guangdong,
China.
3Department of Hematology, Yueqing
People’s Hospital, Yueqing City, 325600, Zhejiang, China
4Department of Obstetrics and Gynecology,
the First Affiliated Hospital of Guangzhou University of Chinese Medicine,
Guangzhou City, 510405, Guangdong, China
Received: 16 July 2024/Accepted:
8 October 2024
#These authors contribute equally
to this work
Abstract
Patients with ulcerative colitis
(UC) are at an increased risk of developing IgG4 related diseases (IgG4-RD).
However, the molecular mechanisms are not known. This study aimed to
investigate the potential molecular mechanisms and drugs to treat both UC and
IgG4-RD. GSE42911 and GSE40568 datasets were intersected to generate common
differentially expressed genes (DEGs). The DEGs were then subjected to Gene
Ontology (GO) and Kyoto Encyclopedia of Genes and
Genomes (KEGG) analysis. After a protein-protein interaction network (PPI)
analysis, hub genes and transcriptional regulators (TFs) were tracked. Finally,
potential therapeutic drugs were predicted by the DGIDB drug database. A total
of 212 common DEGs were identified in between UC and IgG4-RD. Functional
enrichment revealed DEGs enriched in ‘cytoplasm’, and ‘RNA binding’.
Furthermore, KEGG pathway analysis identified significant enrichment in ‘Hippo signaling’. The PPI network was enriched with 162
genes/nodes and 532 edges. Additionally, hub genes and associated with 41 TFs
and 18 miRNAs were found. Finally, 16 potential drugs targeted to four hub
genes were found. In summary, these findings provide novel insights into the
pathophysiology of UC and IgG4-RD, highlighting potential molecular targets and
drug candidates for therapeutic intervention. The identified drugs could pave
the way for targeted therapies, potentially improving clinical outcomes for
patients suffering from these conditions and offering a new direction for
treatment strategies in both UC and IgG4-RD.
Keywords: Bioinformatics; drug molecule; IgG4 related
diseases; protein-protein interaction; ulcerative colitis
Abstrak
Pesakit dengan kolitis ulseratif (UC) mempunyai risiko yang lebih tinggi untuk mendapat penyakit berkaitan IgG4
(IgG4-RD). Walau bagaimanapun, mekanisme molekulnya tidak diketahui. Penyelidikan ini bertujuan untuk mengkaji mekanisme molekul dan dadah yang berpotensi untuk merawat kedua-dua UC dan IgG4-RD.
Dataset GSE42911 dan GSE40568 bersilang untuk menghasilkan gen biasa terekspres secara berbeza (DEG). DEG kemudiannya tertakluk kepada analisis Ontologi Gen (GO) dan Ensiklopedia Gen dan Genom Kyoto (KEGG). Selepas analisis rangkaian interaksi protein-protein (PPI), gen hab dan pengawal selia transkrip (TF) telah dijejaki. Akhirnya, dadah terapeutik yang berpotensi telah diramalkan oleh pangkalan data dadah DGIDB. Sebanyak 212 DEG biasa dikenal pasti antara UC dan IgG4-RD. Pengayaan berfungsi menunjukkan DEG
yang diperkaya dalam ‘sitoplasma’ dan ‘pengikatan RNA’. Tambahan pula, analisis laluan KEGG mengenal pasti pengayaan yang ketara dalam ‘Isyarat Hippo’. Rangkaian PPI telah diperkaya dengan 162
gen/nod dan 532 segi. Selain itu, gen hab dan dikaitkan dengan 41 TF dan 18
miRNA ditemui. Akhirnya, 16 dadah berpotensi yang disasarkan kepada empat gen hab ditemui. Ringkasnya, penemuan ini memberikan pandangan baharu tentang patofisiologi UC dan
IgG4-RD, menonjolkan sasaran molekul yang berpotensi dan calon dadah untuk campur tangan terapeutik. Dadah yang dikenal pasti boleh membuka jalan untuk terapi bersasar yang berpotensi meningkatkan hasil klinikal untuk pesakit yang mengalami keadaan ini dan menawarkan arah baharu untuk strategi rawatan dalam kedua-dua UC dan IgG4-RD.
Kata kunci: Bioinformatik; interaksi protein-protein; kolitis ulseratif; molekul dadah; penyakit berkaitan IgG4
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*Corresponding author; email:
pheng84@163.com
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