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B3GNT3, a Direct Target of miR-149-5p, Promotes Lung Cancer Development and Indicates Poor Prognosis of Lung Cancer

Authors Sun Y, Liu T, Xian L, Liu W, Liu J, Zhou H

Received 29 October 2019

Accepted for publication 24 February 2020

Published 31 March 2020 Volume 2020:12 Pages 2381—2391


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Yong Teng

Yu Sun,1,* Tao Liu,1,* Lei Xian,1 Wenzhou Liu,1 Jun Liu,2 Huafu Zhou2

1Department of Cardio-Thoracic Surgery, The Second Affiliated Hospital of Guangxi Medical University, Guangxi, People’s Republic of China; 2Department of Cardio-Thoracic Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Huafu Zhou
Department of Cardio-Thoracic Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi, People’s Republic of China

Background: B3GNT3 (β 1, 3-N-acetylglucosaminyltransferase-3) belongs to the β 3GlcNAcT family and is essential to form extended core 1 oligosaccharides. Previous studies revealed that B3GNT3 expression was dysregulated in multiple cancers. Here, we aimed to understand the expression profile and function of B3GNT3 in lung cancer.
Materials and Methods: The expression of B3GNT3 was measured by immunohistochemistry and public database analysis. B3GNT3 was knocked down to evaluate the lung cancer cell proliferation, migration and invasion in in vitro and in vivo tumor formation experiments. miR-149-5p targeting B3GNT3 was identified with TargetScan analysis and confirmed with reporter assay. Overexpression of miR-149-5p was achieved using microRNA mimics and function of microRNA-149-5p/B3GNT3 axis was tested in vitro.
Results: B3GNT3 was upregulated in lung cancer, and B3GNT3 overexpression was associated with poor prognosis of lung cancer patients. High expression of B3GNT3 was associated with advanced TNM stages, larger tumor size, tumor metastasis and recurrence. Functionally, we demonstrated that knockdown of B3GNT3 suppressed lung cancer cell growth and invasion in vitro. Knockdown of B3GNT3 suppressed lung cancer development in a xenograft tumor model. Moreover, miR-149-5p was validated to negatively regulate B3GNT3 expression through directly targeting B3GNT3 3ʹ-UTR. Overexpression of miR-149-5p could antagonize the tumorigenesis effect of B3GNT3 in vitro.
Conclusion: In summary, our study demonstrated that B3GNT3 overexpression was correlated with poor prognosis of lung cancer patient, indicating that B3GNT3 could be a promising prognostic biomarker for lung cancer. miR-149-5p negatively regulated B3GNT3 expression, which might be utilized for therapeutic target in lung cancer.

Keywords: B3GNT3, lung cancer, miR-149-5p, tumor progression

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