Table 2.
Research on miRNA and how it relates to HSCR.
| No | Researcher | Years | Sample | Method | Result | Conclusion |
|---|---|---|---|---|---|---|
| 1. | Tang et al. [148] | 2013 | 70 HSCR colon and 60 controls | RT-PCR, western blot, MTT assay and flow cytometry |
↓miR-141, ↑CD47, ↑CUL3 in HSCR (p < 0.05) | An aberrant drop of miR-141 plays a role in pathogenesis of HSCR with inhibits cell migration and cell proliferation |
| 2. | Zhou et al. [133] | 2013 | 73 pairs of colon/rectal tissue specimens, including HSCR stenotic, HSCR dilatation, and normal tissue | qRT-PCR, Western blot | ↓MeCP2 in a HSCR tissue. miRNA-34b expression not affected (p < 0.05) | MeCP2 expression level may play an important role in the pathogenesis of HSCR by decreasing proliferation |
| 3. | Tang et al. [141] | 2014 | 95 HSCR serum and 104 controls | Taqman low density array, qRT-PCR | ↑miR-133a, ↑miR-218-1, ↑miR-92a, ↑miR-25, ↑miR-483-5p (p < 0.05) |
5 types of miRNAs in the serum as HSCR markers have the potential to be a non-invasive diagnostic tool for initial HSCR screening |
| 4. | Mi et al. [149] | 2014 | 50 HSCR patients | ↑miR-124 in aganglionic colon | miR-124 and SOX9 target gene is overexpressed in the aganglionic colon | |
| 5. | Zhu et al. [150] | 2014 | 254 HSCR cases and 265 controls | SNP genotyping (rs2910164, rs11614913), qRT-PCR | The expression of miR-146a is higher for GG than CC genotype; G allele of rs2910164 is associated with HSCR (p < 0.005 OR, 1.54; 95% CI, 1.06–2.23). | G allele of rs2910164 is a risk factor for HSCR, increasing miR-146a expression and decreasing the expression of ROB O 1 which might affect cell proliferation and migration of NCCs |
| 6. | Li et al. [151] | 2014 | 88 HSCR cases and 75 controls | qRT-PCR, western blot | ↓miR-200a & miR141 associated with ↑ PTEN mRNA and protein (p < 0.05) | Family of miR200 might play important roles in the pathogenesis of HSCR with coregulator PTEN. |
| 7. | Lei et al. [152] | 2014 | 78 HSCR colon samples and 66 controls | Cell counting kit 8(CCK-8) | ↑miR-195 in HSCR (p < 0.05) | Aberrant expression of miR-195 might be involved in the pathogenesis HSCR by ↓ DIEXF expression level. |
| 8. | Sharan et al. [147] | 2015 | 80 stenotic HSCR colon samples, 80 dilated HSCR colon samples, and 80 controls | qRT-PCR, western blot, transwell assay, CCK8 assay, flow cytometry, dual- luciferase reporter assays | ↓miR-206 in HSCR compared to control (p < 0.05), ↑SDPR | miR-206 inhibitor suppresses cell migration and proliferation without affecting cell cycle and apoptosis; silencing of SDPR can reduce the extent of the suppressive effect of the miR-206 inhibitor. |
| 9. | Gao et al. [143] | 2017 | 6 HSCR colon samples and 3 controls | Data set screening GSE77296, target gene prediction by miRWalk, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and gene ontology (GO) term analyses, DEM-target gene interaction network analysis |
↑miR-141-3p ↓miR-30a-3p |
Two miRNAs (miR-141-3p and miR-30a-3p), MAPK signaling pathway, and two major genes (FZD3 and DOK6) involved in the pathogenesis of HSCR |
| 10. | Tang et al. [153] | 2015 | 69 HSCR (42 S-HSCR, 27 L-HSCR) 49 controls |
qRT-PCR, Western blot, cell proliferation, cell cycle, and apoptosis, transwell assay, dual luciferase reporter assays | ↑miR-218-1 ↑SLIT2 ↓RET, PLAG1 (p < 0.05) |
Overexpression of SLIT2 inhibits cell migration by binding to ROB O 1 receptor |
| 11. | Zhu et al. [154] | 2015 | 80 HSCR colon samples and 77 controls | qRT-PRC western blot, a dual-luciferase reporter assay, transwell assay, CCK8 assay, flow cytometry |
↓miR-192/215 in HSCR (p = 0.0001) ↑Nidogen1 (NID1) |
Reduced mir-192/215 inhibits cell migration and proliferation; silencing of NID1 can reduce the extent of the suppressive effect of miR-192/215 inhibitor |
| 12. | Li et al. [140] | 2016 | 76 HSCR colon samples and 3 control | miRNA target prediction by miRWalk software, qRT-PCR |
Significant (p < 0,05) Upregulated ↑: miR-142-3p, miR-142-5p, miR-146b-5p, miR-369-3p, dan miR-429. Downregulated ↓: miR-885-3p. (p < 0.05) | miRNA play important roles in the complex and multifactorial pathophysiology of HSCR |
| 13. | Lei et al. [155] | 2016 | 70 HSCR colon samples and 62 controls | qRT-PCR, western blot, dual-luciferase reporter assay, transwell assay, CCK8 assay, flow cytometry | ↓miR-215, ↑Sialic acid binding Ig-like lectin 8 (SIGLEC-8) (p < 0.05) |
miR-215 causes SIGLEC-8 inhibition by binding directly to the 3′-UTR region of SIGLEC-8 Silencing of SIGLEC-8 can reduce the extent of the effect of suppressing cell migration and proliferation due to the decline of miR-215 IARS2-miR-215-SIGLEC-8 pathway might play role in the pathogenesis of HSCR |
| 14. | Pan et al. [145] | 2017 | 60 HSCR colon samples and 47 controls | qRT-PCR, dual-luciferase reporter assay, transwell assay, CCK8 assay, flow cytometry | ↑miR-369-3p, ↓SOX4 (p < 0.05) | Aberrant expression of miR-369-3p may be involved in the pathogenesis of HSCR by regulating the expression of SOX4; dysregulation of miR-369-3p and SOX4 suppresses cell migration and proliferation |
| 15. | Wang et al. [156] | 2017 | 20 HSCR colon samples and 20 controls | qRT-PCR, western blot, dual-luciferase reporter assay, transwell assay, CCK8 assay, flow cytometry | ↑miR-483-5p, ↓GFRA4 (p < 0.05) |
miR-483-5p plays a role in the pathogenesis of HSCR with the target gene GFRA4 Downregulation of miR-483-5p increases cell proliferation, cell cycle, cell invasion, and inhibit cell apoptosis |
| 16. | Wu et al. [144] | 2018 | 24 HSCR colon samples and 20 controls | qRT-PCR, western blot, dual-luciferase reporter assay, transwell assay, CCK8 assay, flow cytometry | ↑miR-214, ↓PLAGL2 (p < 0.001) | miR-214 plays a role in the pathogenesis of HSCR by inhibiting cell migration and proliferation by directly decreasing PLAGL2 expression |
| 17. | Hu et al. [157] | 2018 | 8 HSCR colon samples and 8 controls | qRT-PCR, western blotting, CCK-8 assay, luciferase reporter assay | ↑miR-431-5p, ↓LRSAM1 | Reduced mir-431-5p support ENCCs proliferation by targeting LRSAM1 |
| 18. | Gunadi, et al. [146] | 2019 | 21 HSCR ganglionic (G), aganglionic (A), and 13 controls | qRT-PCR | ↑miRNA-206 (2-fold) in HSCR-G and↓(0.5-fold) in HSCR-A (p = 0.48 and p = 0.46). ↑FN1 (38-fold) in HSCR-G and ↓(18-fold) in HSCR-A (p = 0.001 and p = 0.038). |
Aberrant expression of FN1 may play role in the pathogenesis of HSCR |
| 19. | Lv et al. [158] | 2020 | 48 HSCR blood plasma samples and 48 controls | qRT-PCR, western blotting | ↑miR-494-3p, miR-668-3p, miR-3231-3p, and miR-605-3p ↓miR-5701 (p < 0.01) |
Those five miRNAs are significant markers for HSCR diagnostics |