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TÜRKÇE
Oral Presentation - 106
miRNA-Mediated Pathogenic Mechanisms in Hirschsprung Disease: Insights from Next-Generation Sequencing-Based Tissue Profiling
Khanza Adzkia Vujira 1, Pramana Adhityo 1, Dyah Ayu Puspitarani 1, Marcellus - 1, William Widitjiarso 1, Afiahayati - 2, Kristy Iskandar 3, Husna Nugrahapraja 4, Gunadi - 1
1 Pediatric Surgery Division, Department of Surgery/Genetics Working Group, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/Dr.Sardjito Hospital
2 Department of Computer Science and Electronics, Faculty of Mathematics and Natural Sciences, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia
3 Department of Child Health, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada/UGM Academic Hospital, Yogyakarta 55291, Indonesia
4 School of Life Science and Technology, Institut Teknologi Bandung, Bandung 40132, Indonesia
Purpose: Hirschsprung disease (HSCR) is characterized by the absence of neuronal ganglia in the intestine. While pathogenic variants in genes such as RET, GDNF, and EDNRB account for 80% of cases, the remaining 20% is poorly understood. MicroRNAs are critical regulators of gene expression in the development of the nervous system, which may influence the pathogenesis of HSCR. This study aimed to examine the tissue miRNA profiles of HSCR patients to gain new insights into disease mechanisms.
Methods: Fresh colon tissue samples were collected from ten HSCR patients and two controls. Total RNA was isolated, and miRNA libraries were prepared and sequenced using the Illumina miSeq platform, employing 50 bp single-end reads. The sequenced miRNAs were analyzed using miRDeep2, referencing four databases to categorize the outputs into mature miRNAs, isomiRs, and piRNAs. Differentially expressed miRNA profiles were identified following data preprocessing.
Results: Eleven unique miRNA families were identified in HSCR tissues, including miRNA-143, miRNA-192, and miRNA-770, which were upregulated compared to the controls. Notably, hsa-mir-1248 was the most abundant miRNA , appearing in six samples with the highest total read count. Rare miRNAs, such as hsa-mir-3648-1 and hsa-mir-3648-2, were identified in individual samples, suggesting specific expression patterns. Interestingly, miRNA-192 showed upregulation in HSCR tissues, contradicting previous reports and was associated with Nidogen 1, a gene essential for the development of the enteric nervous system. Additionally, miRNA-770 supported earlier findings by acting through the MEG3/miR-770-5p/SRGAP1 pathway, highlighting its potential as a therapeutic target.
Conclusions: Our study is the first to profile miRNAs in Indonesian HSCR patients, identifying key miRNAs involved in its pathogenesis. These findings enhance our understanding of HSCR and highlight the diversity of miRNAs and their crucial roles in the disease's development.