Downregulation of miR-140-5p affects the pathogenesis of HSCR by targeting EGR2

被引:7
作者
Du, Guoqiang [1 ]
Wang, Xiaoqing [1 ]
Wu, Yidi [1 ]
Zhang, Yongfei [2 ]
Liu, Wei [1 ]
Wu, Rongde [1 ]
机构
[1] Shandong Univ, Dept Pediat Surg, Shandong Prov Hosp, 324 Jingwu St, Jinan 250021, Shandong, Peoples R China
[2] Shandong First Med Univ, Dept Dermatol, Affiliated Hosp 1, Jinan, Peoples R China
关键词
EGR2; Hirschsprung's disease; SH-SY5Y; Apoptosis; miR-140-5p; HIRSCHSPRUNGS-DISEASE; CELL-PROLIFERATION; GROWTH; GENES; TUMOR; DIFFERENTIATION; PROGRESSION; EXPRESSION; MICRORNAS; APOPTOSIS;
D O I
10.1007/s00383-020-04686-0
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Background/aims Hirschsprung's disease (HSCR) is the most common digestive disease caused by disorders of neural crest development. Despite the known involvement of miR-140-5p in many human diseases, its biological role in Hirschsprung's disease (HSCR) remains undefined. In this study, we sought to reveal the roles of miR-140-5p in the pathogenesis of HSCR. Methods Quantitative real-time PCR and western blotting were used to measure the relative expression levels of miRNAs, mRNAs, and proteins in stenotic and dilated sections of the colon of 32 HSCR patients. Targets and proteins were evaluated by western blotting, and Transwell, CCK-8, and flow cytometry assays were adopted to detect the functional effects of miR-140-5p on SH-SY5Y cells. Results miR-140-5p was significantly downregulated in HSCR tissue samples with increased expression of EGR2, and knockdown of miR-140-5p inhibited cell migration and proliferation and promoted apoptosis in SH-SY5Y cell lines. EGR2 expression was inversely correlated with that of miR-140-5p in cell lines. Conclusions miR-140-5p may influence the pathogenesis of HSCR by targeting EGR2.
引用
收藏
页码:883 / 890
页数:8
相关论文
共 38 条
[1]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[2]   Hirschsprung's disease and variants in genes that regulate enteric neural crest cell proliferation, migration and differentiation [J].
Carter, Tonia C. ;
Kay, Denise M. ;
Browne, Marilyn L. ;
Liu, Aiyi ;
Romitti, Paul A. ;
Kuehn, Devon ;
Conley, Mary R. ;
Caggana, Michele ;
Druschel, Charlotte M. ;
Brody, Lawrence C. ;
Mills, James L. .
JOURNAL OF HUMAN GENETICS, 2012, 57 (08) :485-493
[3]   Negative feedback circuitry between MIR143HG and RBM24 in Hirschsprung disease [J].
Du, Chunxia ;
Shen, Ziyang ;
Zang, Rujin ;
Xie, Hua ;
Li, Hongxing ;
Chen, Pingfa ;
Hang, Bo ;
Xu, Xiaoqun ;
Tang, Weibing ;
Xia, Yankai .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 2016, 1862 (11) :2127-2136
[4]   A common sex-dependent mutation in a RET enhancer underlies Hirschsprung disease risk [J].
Emison, ES ;
McCallion, AS ;
Kashuk, CS ;
Bush, RT ;
Grice, E ;
Lin, S ;
Portnoy, ME ;
Cutler, DJ ;
Green, ED ;
Chakravarti, A .
NATURE, 2005, 434 (7035) :857-863
[5]   Dual function of the PI3K-Akt-mTORC1 axis in myelination of the peripheral nervous system [J].
Figlia, Gianluca ;
Norrmen, Camilla ;
Pereira, Jorge A. ;
Gerber, Daniel ;
Suter, Ueli .
ELIFE, 2017, 6
[6]  
Ganz J, 2018, DEV DYNAM, V247, P268, DOI [10.1002/DVDY.24597, 10.1002/dvdy.24597]
[7]   Open Versus Transanal Pull-Through for Hirschsprung Disease: A Systematic Review of Long-Term Outcome [J].
Gosemann, Jan-Hendrik ;
Friedmacher, Florian ;
Ure, Benno ;
Lacher, Martin .
EUROPEAN JOURNAL OF PEDIATRIC SURGERY, 2013, 23 (02) :94-102
[8]   The role of the gut microbiota in development, function and disorders of the central nervous system and the enteric nervous system [J].
Heiss, Christina N. ;
Olofsson, Louise E. .
JOURNAL OF NEUROENDOCRINOLOGY, 2019, 31 (05)
[9]   Triangle of AKT2, miRNA, and Tumorigenesis in Different Cancers [J].
Honardoost, Maryam ;
Rad, Seyed Mohammad Ali Hosseini .
APPLIED BIOCHEMISTRY AND BIOTECHNOLOGY, 2018, 185 (02) :524-540
[10]   Hirschsprung's disease [J].
Kenny, Simon E. ;
Tam, Paul K. H. ;
Garcia-Barcelo, Merce .
SEMINARS IN PEDIATRIC SURGERY, 2010, 19 (03) :194-200