4.7 Article

B4GALT3 up-regulation by miR-27a contributes to the oncogenic activity in human cervical cancer cells

Journal

CANCER LETTERS
Volume 375, Issue 2, Pages 284-292

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.03.016

Keywords

B4GALT3; miR-27a; EMT; beta 1-integrin; Cervical cancer cells

Categories

Funding

  1. National Natural Science Foundation of China [91029714, 31071191, 31270818, 81572790]
  2. Natural Science Foundation of Tianjin [12JCZDJC25100]

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beta-1,4-Galactosyltransferase III (B4GALT3) is an enzyme responsible for the generation of poly-N-acetyllactosamine and is involved in tumorigenesis. However, B4GALT3-dysregulation and its role in cervical cancer cells are unknown. Herein, we found that B4GALT3 was upregulated in cervical cancer tissues compared to adjacent non-tumor tissues. B4GALT3-overexpression promoted, whereas B4GALT3-knockdown suppressed the cellular migration, invasion and EMT of HeLa and C33A cervical cancer cells. To explore the mechanism of dysregulation, B4GALT3 was predicted to be a target of miR-27a. EGFP and pGL3-promoter reporter assay showed miR-27a binds to B4GALT3 3'UTR region but enhanced its expression. RT-qPCR showed miR-27a was also upregulated and presented positive correlation with B4GALT3-expression in cervical cancer tissues. miR-27a-overexpression promoted, but blocking-miR-27a repressed these malignancies in HeLa and C33A cells. Furthermore, shR-B4GALT3 counteracted the promotion of malignancies induced by miR-27a, suggesting miR-27a upregulates B4GALT3 to enhance tumorigenic activities. In addition, we found that B4GALT3 significantly enhances beta 1-integrin stability, thus mediating promotion of B4GALT3 on malignancy in cervical cancer cells. Altogether, our findings evidenced that B4GALT3 upregulated by miR-27a contributes to the tumorigenic activities by P1-integrin pathway and might provide potential biomarkers for cervical cancer. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

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