Abstract
BackgroundMicroRNAs (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.MethodsWe 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).ResultsTwenty-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 (ΔCT 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 ΔCT 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 (ΔCT 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 (ΔCT 3.8 ± 0.8 vs. 4.1 ± 0.8 vs. 3.7 ± 1.1; p = 0.83 and p = 0.44, respectively).ConclusionOur 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.
Highlights
MicroRNAs have been associated with the Hirschsprung disease (HSCR) pathogenesis, the findings are still inconclusive
At least 15 genes have been associated with the pathogenesis of HSCR, with the RET gene as primarily
The ganglionic and aganglionic colon of HSCR patients were collected at definitive surgery, while the control colon samples were obtained at stoma closure from anorectal malformation patients [12]
Summary
MicroRNAs (miRNAs) have been associated with the Hirschsprung disease (HSCR) pathogenesis, 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. Hirschsprung disease (HSCR: MIM# 142623) is a complex genetic disorder characterized by the absence of ganglion cells in the intestines, resulting in a functional obstruction in children. At least 15 genes have been associated with the pathogenesis of HSCR, with the RET gene as primarily miRNA-206 has been shown to be down-regulated and targeted three genes, named fibronectin 1 (FN1), serum deprivation response (SDPR), and paired box 3 (PAX3), in HSCR patients in Chinese population [7]. Some genetic differences might exist among Asian population [9] and our previous study revealed that the impact of SEMA3 rs11766001 variant differs among ethnic
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