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

Abstract

β-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.

Identifying the key genes and microRNAs in prostate cancer bone metastasis by bioinformatics analysis

“…In the network, miR‐199b‐5p, miR‐199b‐3p and miR‐636 had rich external connections. Studies had reported that the miR‐199 family, as a tumor suppressor, inhibited tumor growth and metastasis [39–43]. Our group also found that miR‐199b‐5p suppressed cell proliferation, migration and invasion by down‐regulating DDR1 in PCa (S. H. Zhao, L. M. Luo, X. Qian, Z. G. Zhu, J. M. Wang, Y.…”

A Systematic Review on the Implications of O-linked Glycan Branching and Truncating Enzymes on Cancer Progression and Metastasis

“…Other than GCNT1 and GCNT3, GCNT2 primarily synthesizes I antigen and is not involved in O-glycosylation. However, because multiple studies suggests its important role in CRC, we chose to describe those studies here [118]. GCNT2 expression is regulated by EGF, bFGF-t, and miR-199 in the regulation of colon carcinoma.…”

Proteomics-Based Evidence for a Pro-Oncogenic Role of ESRP1 in Human Colorectal Cancer Cells

“…On the other hand, Esrp1-silenced HCA24 cells exhibited an increase in eight proteins including Guanine nucleotide exchange factor for Rab-3A (RAB3IL1); Protein FAM49A (FAM49A); N-acetyllactosaminide beta-1,6-N-acetylglucosaminyl-transferase, isoform A (GCNT2), which is induced upon EMT in colon cancer cells; TNFAIP3-interacting protein 2 (TNIP2), which may modulate the microenvironment for colorectal cancer development, and Triosephosphate Isomerase (TPI1) involved in glycolytic metabolism, and a decrease in seven proteins including heat shock protein (HSP) 90-alpha (HSP90AA1), which plays a fundamental role in several cellular processes pertaining to tumorigenesis such as cell proliferation and survival and malignancy such as invasion, angiogenesis and metastasis; Protein Disulfide-isomerase (P4HB) involved in the proliferation, survival, and metastasis of several types of cancer cells; Actin, cytoplasmic 1 (ACTB), a cytoskeletal protein, essential for the structure and kinetics of the cytoskeleton; and DNA repair and recombination protein RAD54-like (RAD54) involved in double-strand break repair ( Figure 2B) [20][21][22][23][24]. Selected candidates were validated by qRT-PCR and western blot, and confirmed the down-regulation of HSP90AA1 at protein level ( Figure 2C), as well as a slight increase inTPI1 at RNA level in HCA24 cells ( Figure 2D).…”