In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 20, No. 7 ( 2016-07), p. 1266-1275
Abstract:
Hirschsprung disease ( HSCR ) is a congenital disorder caused by the defective function of the embryonic enteric neural crest. The impaired migration of embryonic enteric neural crest plays an important role in the pathogenesis of this disease. Recent studies showed that the ARP 2/3 complex and RAC isoforms had effects on actin cytoskeleton remodelling, which contributes to migration. Moreover, some regulatory relationships were identified between ARP 2/3 complex and RAC isoforms. Although micro RNA s (mi RNA s) have been known to modulate target gene expression on the post‐transcriptional level, little is known about the regulation among mi RNA s, ARP 2/3 complex and RAC isoforms. Here, we report that down‐regulation of ARP 2 and ARP 3, two main subunits of ARP 2/3 complex, suppressed migration and proliferation in 293T and SH ‐ SY 5Y cell lines via the inhibition of RAC 1 and RAC 2. Meanwhile, as the target genes, ARP 2 and ARP 3 are reduced by increased miR‐24‐1* and let‐7a*, respectively, in 70 HSCR samples as compared with 74 normal controls. Co‐immunoprecipitation showed that aberrant reduction in ARP 2 and ARP 3 could weaken the function of ARP 2/3 complex. Our study demonstrates that the miR‐24‐1*/let‐7a*‐ ARP 2/3 complex‐ RAC isoforms pathway may represent a novel pathogenic mechanism for HSCR .
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2016.20.issue-7
Language:
English
Publisher:
Wiley
Publication Date:
2016
detail.hit.zdb_id:
2076114-4
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