Dataset Information

Aberrant expressions of miRNA-206 target, FN1, in multifactorial Hirschsprung disease.

ABSTRACT: BACKGROUND:MicroRNAs (miRNAs) have been associated with the Hirschsprung disease (HSCR) pathogenesis, however, the findings are still inconclusive. We aimed to investigate the effect of miRNA-206 and its targets, fibronectin 1 (FN1), serum deprivation response (SDPR), and paired box 3 (PAX3) expressions on multifactorial HSCR in Indonesia, a genetically distinct group within Asia. METHODS:We determined the miRNA-206, FN1, SDPR and PAX3 expressions in both the ganglionic and aganglionic colon of HSCR patients and control colon by quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS:Twenty-one sporadic HSCR patients and thirteen controls were ascertained in this study. The miRNA-206 expression was up-regulated (2-fold) in the ganglionic colon and down-regulated (0.5-fold) in the aganglionic colon compared to the control group (?CT 12.4?±?3.0 vs. 14.1?±?3.9 vs. 13.1?±?2.7), but these differences did not reach significant levels (p =?0.48 and p =?0.46, respectively). Interestingly, the FN1 expression was significantly increased in both the ganglionic (38-fold) and aganglionic colon (18-fold) groups compared to the control group ?CT 5.7?±?3.0 vs. 6.8?±?2.3 vs. 11.0?±?5.0; p =?0.001 and p =?0.038, respectively). Furthermore, the expressions of SDPR were similar in the ganglionic, aganglionic and control colon groups (?CT 2.4?±?0.6 vs. 2.2?±?0.4 vs. 2.1?±?0.6; p =?0.16 and p =?0.39, respectively), while no change was observed in the PAX3 expression between the ganglionic, aganglionic, and control colon groups (?CT 3.8?±?0.8 vs. 4.1?±?0.8 vs. 3.7?±?1.1; p =?0.83 and p =?0.44, respectively). CONCLUSION:Our study is the first report of aberrant FN1 expressions in the colon of patients with HSCR and supplies further insights into the contribution of aberrant FN1 expression in the HSCR pathogenesis.

SUBMITTER: Gunadi

PROVIDER: S-EPMC6323865 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Aberrant expressions of miRNA-206 target, FN1, in multifactorial Hirschsprung disease.

Gunadi Budi Nova Yuli Prasetyo NYP Kalim Alvin Santoso AS Santiko Wiwid W Musthofa Fuad Dheni FD Iskandar Kristy K Makhmudi Akhmad A

Orphanet journal of rare diseases 20190107 1

<h4>Background</h4>MicroRNAs (miRNAs) have been associated with the Hirschsprung disease (HSCR) pathogenesis, however, the findings are still inconclusive. We aimed to investigate the effect of miRNA-206 and its targets, fibronectin 1 (FN1), serum deprivation response (SDPR), and paired box 3 (PAX3) expressions on multifactorial HSCR in Indonesia, a genetically distinct group within Asia.<h4>Methods</h4>We determined the miRNA-206, FN1, SDPR and PAX3 expressions in both the ganglionic and agangl ...[more]

PMID: 30616633

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Project description:BackgroundHirschsprung disease (HSCR) is a complex genetic disorder characterized by the lack of ganglion cells in the intestines. A current study showed that the NRG1 rare variant frequency in Indonesian patients with HSCR is only 0.9%. Here, we investigated the impact of NRG1 expressions and methylation patterns on the pathogenesis of HSCR.MethodsThis cross-sectional study determined NRG1 type I (HRGα, HRGβ1, HRGβ2, HRGβ3, HRGγ, and NDF43 isoforms), type II and type III expressions in both ganglionic and aganglionic colons of 20 patients with HSCR and 10 control colons by real-time polymerase chain reaction (qPCR). For methylation studies, we treated the extracted gDNA from 16 HSCR patients' and 17 control colons with sodium bisulfate and analyzed the methylation pattern of NRG1 exon 1 with methylation-specific PCR. The samples were collected and analyzed at our institution from December 2018 to December 2020.ResultsNRG1 types I, II and III expressions were upregulated (17.2-, 3.2-, and 7.2-fold, respectively) in the ganglionic colons compared with control colons (type I: 13.32 ± 1.65 vs. 17.42 ± 1.51, p < 0.01; type II: 13.73 ± 2.02 vs. 16.29 ± 2.19, p < 0.01; type III: 13.47 ± 3.01 vs. 16.32 ± 2.58, p = 0.03; respectively); while only type I (7.7-fold) and HRGβ1/HRGβ2 (3.3-fold) isoforms were significantly upregulated in the aganglionic colons compared to the controls (type I: 14.47 ± 1.66 vs. 17.42 ± 1.51, p < 0.01; HRGβ1/HRGβ2: 13.62 ± 3.42 vs 14.75 ± 1.26, p = 0.01). Moreover, the frequency of partially methylated NRG1 was higher in the ganglionic (81%) and aganglionic (75%) colons than in the controls (59%).ConclusionsOur study provides further insights into the aberrant NRG1 expression in the colons of patients with HSCR, both ganglionic and aganglionic bowel, which might contribute to the development of HSCR, particularly in Indonesia. Furthermore, these aberrant NRG1 expressions might be associated with its methylation pattern.

Dataset Information

Aberrant expressions of miRNA-206 target, FN1, in multifactorial Hirschsprung disease.

Publications

Aberrant expressions of miRNA-206 target, FN1, in multifactorial Hirschsprung disease.

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