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Downregulation of HDGF inhibits the tumorigenesis of bladder cancer cells by inactivating the PI3K-AKT signaling pathway

Authors Zhang C, Chang X, Chen D, Yang F, Li Z, Li D, Yu N, Yan L, Liu H, Xu Z

Received 11 May 2019

Accepted for publication 28 June 2019

Published 22 August 2019 Volume 2019:11 Pages 7909—7923

DOI https://doi.org/10.2147/CMAR.S215341

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 2

Editor who approved publication: Dr Chien-Feng Li


Cong Zhang,1,2 Xiangping Chang,1 Dongshan Chen,1 Feilong Yang,3 Zeyan Li,1 Dawei Li,1 Nengwang Yu,1 Lei Yan,1 Hainan Liu,1 Zhonghua Xu1

1Department of Urology, Qilu Hospital of Shandong University, Jinan 250012, People’s Republic of China; 2Key Laboratory of Cardiovascular Remodeling and Function Research, Shandong University, Jinan, People’s Republic of China; 3Department of Urology, Peking University Third Hospital, Beijing 100191, People’s Republic of China

Correspondence: Dawei Li
Department of Urology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan 250012, People’s Republic of China
Tel +86 5 318 216 6701
Fax +86 5 318 216 9044
Email lidaweimd@aliyun.com

Background: Hepatoma-derived growth factor (HDGF) is a heparin-binding protein that has been observed to be abnormally expressed in numerous malignancies, but the definite role of HDGF in bladder cancer (BCa) has not been clarified. Here, we conduct the present study to evaluate correlations between HDGF and BCa.
Methods: Bioinformatics analysis was used to evaluate HDGF expression levels in BCa tissues. The effect of HDGF on cell proliferation, migration, invasion, cell cycle and apoptosis was analyzed utilizing CCK-8, clone formation, Transwell assays and flow cytometry, respectively. In addition, the xenograft tumor model was established.
Results: Based on bioinformatics analysis, we noticed that HDGF was highly expressed in BCa tissues and was positively correlated with poor prognosis in patients. Knockdown of HDGF markedly reduced tumorigenesis in BCa cells. Furthermore, the results of flow cytometry showed that HDGF deletion enhanced apoptosis in T24 and 253J cells and led to cell cycle arrest in G1 phase. In further studies, we found that tumor growth was inhibited in xenograft nude mouse models with HDGF deletion. The results of RNA-seq analysis revealed that the PI3K-AKT signaling pathway-related genes were obviously changed in HDGF-deficient 253J cells, and this result was further confirmed by Western blot analysis.
Conclusion: In summary, we suggest that HDGF plays a substantial role in BCa and promotes tumor development and progression by regulating the PI3K-AKT signaling pathway, which provides a promising target for BCa treatment.

Keywords: HDGF, bladder cancer, tumorigenesis, PI3K/AKT signaling


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