Downregulation of miR-199a/b-5p is associated with GCNT2 induction upon epithelial-mesenchymal transition in colon cancer

被引：37

作者：

Chao, Chia-Chun ^{[1
,2
]}

Wu, Po-Han ^{[2
]}

Huang, Hsiang-Chi ^{[2
,3
,4
]}

Chung, Hsiao-Yu ^{[2
]}

Chou, Yu-Chi ^{[5
,6
]}

Cai, Bi-He ^{[2
,7
]}

Kannagi, Reiji ^{[1
,2
]}

机构：

[1] Natl Def Med Ctr, Grad Inst Life Sci, Taipei, Taiwan

[2] Acad Sinica, Inst Biomed Sci, 128 Sec 2,Acad Rd, Taipei 115, Taiwan

[3] Natl Yang Ming Univ, Taiwan Int Grad Program Mol Med, Taipei, Taiwan

[4] Acad Sinica, Taipei, Taiwan

[5] Acad Sinica, Genom Res Ctr, Taipei, Taiwan

[6] Acad Sinica, Natl RNAi Core Facil, Taipei, Taiwan

[7] Natl Def Med Ctr, Dept Biol & Anat, Taipei, Taiwan

来源：

FEBS LETTERS | 2017年 / 591卷 / 13期

关键词：

cancer; EMT; GCNT2; I antigen glycan; microRNA; miR-199; MOLECULAR-GENETICS; STEM-CELLS; EXPRESSION; METASTASIS; GLYCOSYLATION; MECHANISMS; MICRORNAS; SUPPRESS; INVASION; ACTIVATION;

D O I：

10.1002/1873-3468.12685

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

beta-1,6-N-acetylglucosaminyltransferase 2 (GCNT2), which encodes a key glycosyltransferase for blood group I antigen synthesis, is induced upon epithelial-mesenchymal transition (EMT). Our results indicate that GCNT2 is upregulated upon EMT induced with epidermal growth factor and basic FGF in cultured human colon cancer cells. GCNT2 knockdown or overexpression decreases or increases, respectively, malignancy-related characteristics of colon cancer cells and I antigen levels. MiR-199a/b-5p is markedly downregulated upon EMT in colon cancer cells. Here, we find that miR-199a/b-5p consistently regulates GCNT2 expression in reporter assays and that it binds directly to the GCNT2 3' untranslated region intracellularly in RNA-induced silencing complex-trap assays. Overexpression of miR-199a/b-5p decreases GCNT2 expression and suppresses I antigen production. Based on these findings, we propose that miR-199a/b-5p regulates GCNT2 and I antigen expression in colon cancer cells undergoing EMT.

引用

页码：1902 / 1917

页数：16

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