Suppressive action of mi RNA s to ARP 2/3 complex reduces cell migration and proliferation via RAC isoforms in Hirschsprung disease
Authors: Bo Hang
Shouyu Wang
Hua Xie
Yankai Xia
Peng Cai
Pingfa Chen
Weiwei Huo
Junwei Tang
Dongmei Zhu
Weibing Tang
Hongxing Li
Journal: Journal of Cellular and Molecular Medicine (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ARP2/3 complex; Hirschsprung disease; RAC isoforms; gene regulation; microRNA.
Affiliations: Department of Pediatric Surgery, Nanjing Children's Hospital Affiliated Nanjing Medical University, Nanjing, China., State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing, China., Children's Hospital of Soochow University, Soochow, China., Key Laboratory of Modern Toxicology (Nanjing Medical University), Ministry of Education, Nanjing, China., Department of Cell and Molecular Biology, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA., Department of Molecular Cell Biology and Toxicology, Jiangsu Key Lab of Cancer Biomarkers, Prevention & Treatment, Cancer Center, School of Public Health, Nanjing Medical University, Nanjing, China.

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 ARP2/3 complex and RAC isoforms had effects on actin cytoskeleton remodelling, which contributes to migration. Moreover, some regulatory relationships were identified between ARP2/3 complex and RAC isoforms. Although microRNAs (miRNAs) have been known to modulate target gene expression on the post-transcriptional level, little is known about the regulation among miRNAs, ARP2/3 complex and RAC isoforms. Here, we report that down-regulation of ARP2 and ARP3, two main subunits of ARP2/3 complex, suppressed migration and proliferation in 293T and SH-SY5Y cell lines via the inhibition of RAC1 and RAC2. Meanwhile, as the target genes, ARP2 and ARP3 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 ARP2 and ARP3 could weaken the function of ARP2/3 complex. Our study demonstrates that the miR-24-1*/let-7a*-ARP2/3 complex-RAC isoforms pathway may represent a novel pathogenic mechanism for HSCR. 

Retracted: No

PubPeer comments:
 September 2018 Correction, which reads:  In Tang et al,1 the original article contains incorrect Fig. 3A. The correct version of Figure 3 (Panel A) should have been as depicted below, all of the results and conclusions of the article remain unchanged. Here is the original version of Figure 3A, marked by an image forensics tool for duplications. There appear to be a lot of duplications in the original figure - casting doubt over reliability of other data in this paper. ![file] , 
 #1 Thank you very much for your attention and guidance. We have carefully checked and confirmed the accuracy of the data results and conclusions, and published the corrigendum (https: pubmed.ncbi.nlm.nih.gov 30255618 uff09. In order to further enhance the rigor of our research, we have improved the management of research data and the preservation of images. If you have any other questions, please contact the relevant email. Thanks again for your kindly reminder. ,