Open AccessSuppressive action of mi RNA s to ARP 2/3 complex reduces cell migration and proliferation via RAC isoforms in Hirschsprung disease
Author(s) -
Tang Weibing,
Cai Peng,
Huo Weiwei,
Li Hongxing,
Tang Junwei,
Zhu Dongmei,
Xie Hua,
Chen Pingfa,
Hang Bo,
Wang Shouyu,
Xia Yankai
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12799
Subject(s) - gene isoform , biology , microbiology and biotechnology , neural crest , rna binding protein , immunoprecipitation , rna , gene , genetics , embryo
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 .