Hsa-miR-11181 regulates Wnt signaling pathway through targeting of APC2 transcripts in SW480 cell line

被引:10
作者
Dokanehiifard, Sadat [1 ]
Soltani, Bahram M. [1 ]
机构
[1] Tarbiat Modares Univ, Fac Biol Sci, Dept Mol Genet, Tehran, Iran
基金
美国国家科学基金会;
关键词
hsa-miR-11181; Wnt signaling pathway; APC1; APC2; Axin1; RECEPTOR-RELATED PROTEIN-5; PLAKOGLOBIN; EXPRESSION;
D O I
10.1016/j.gene.2017.10.075
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Wnt signaling plays important roles in differentiation, morphogenesis and development. This signaling pathway is highly regulated at all levels and microRNAs are small noncoding RNAs regulating Wnt signaling. Here, we intended to investigate hsa-miR-11181 (a novel miRNA located in TrkC gene) effect on Wnt signaling pathway in SW480 cell line. TOP/FOP flash assay indicated up-regulation of Wnt signaling, following the overexpression of hsa-miR-11181, verified through RT-qPCR. Bioinformatics analysis predicted APC1, APC2 and Axin1 might be targeted by hsa-miR-11181. Then, RT-qPCR analysis indicated that APC2 and Axin1 have been significantly down-regulated following the hsa-miR-11181 overexpression. However dual luciferase assay analysis supported only APC2 3'-UTR is directly targeted by this miRNA. Then, treatment of SW480 cells with Wnt-inhibitory small molecules supported the effect of hsa-miR-11181 at the inhibitory complex level containing APC2 protein. Consistently, viability of SW480 cells overexpressing hsa-miR-11181 was significantly elevated, measured through MIT assay. Overall, these results suggest that hsa-miR-11181 may play a crucial role in Wnt signaling regulation and confirmed that APC2 3'-UTR is targeted by hsa-miR-11181 and propose the presence of its recognition sites in the promoter or coding regions of Axin1 gene.
引用
收藏
页码:297 / 302
页数:6
相关论文
共 24 条
[1]  
[Anonymous], J BIOL CHEM
[2]   Inhibition of Tankyrases Induces Axin Stabilization and Blocks Wnt Signalling in Breast Cancer Cells [J].
Bao, Renyue ;
Christova, Tania ;
Song, Siyuan ;
Angers, Stephane ;
Yan, Xiaojun ;
Attisano, Liliana .
PLOS ONE, 2012, 7 (11)
[3]  
Cammarata PR, 2015, MOL VIS, V21, P1024
[4]   Octreotide inhibits growth of colonic cancer SW480 cells by modulating the Wnt/β-catenin pathway [J].
Chen, Jing-song ;
Liang, Qing-mo ;
Li, Hua-shu ;
Yang, Jie ;
Wang, Song ;
Long, Jian-wu .
PHARMAZIE, 2009, 64 (02) :126-131
[5]   Involvement of the Wnt/β-catenin pathway in neurectoderm architecture in Platynereis dumerilii [J].
Demilly, Adrien ;
Steinmetz, Patrick ;
Gazave, Eve ;
Marchand, Lauriane ;
Vervoort, Michel .
NATURE COMMUNICATIONS, 2013, 4
[6]  
Dokanehiifard S., 2015, CELL MOL LIFE SCI, P1
[7]   Suppression of canonical Wnt/β-catenin signaling by nuclear plakoglobin recapitulates phenotype of arrhythmogenic right ventricular cardiomyopathy [J].
Garcia-Gras, Eduardo ;
Lombardi, Raffaella ;
Giocondo, Michael J. ;
Willerson, James T. ;
Schneider, Michael D. ;
Khoury, Dirar S. ;
Marian, Ali J. .
JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (07) :2012-2021
[8]   Wnt signaling: Multiple pathways, multiple receptors, and multiple transcription factors [J].
Gordon, Michael D. ;
Nusse, Roel .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (32) :22429-22433
[9]   LDL receptor-related proteins 5 and 6 in Wnt/β-catenin signaling:: Arrows point the way [J].
He, X ;
Semenov, M ;
Tamai, K ;
Zeng, X .
DEVELOPMENT, 2004, 131 (08) :1663-1677
[10]   Comprehensive analysis of β-catenin target genes in colorectal carcinoma cell lines with deregulated Wnt/β-catenin signaling [J].
Herbst, Andreas ;
Jurinovic, Vindi ;
Krebs, Stefan ;
Thieme, Susanne E. ;
Blum, Helmut ;
Goeke, Burkhard ;
Kolligs, Frank T. .
BMC GENOMICS, 2014, 15