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

• Main Authors: Zhang C, Chang X, Chen D, Yang F, Li Z, Li D, Yu N, Yan L, Liu H, Xu Z
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-08-01
• Series: Cancer Management and Research
• Subjects: HDGF; Bladder cancer; tumorigenesis; PI3K/AKT signaling
• Online Access: https://www.dovepress.com/downregulation-of-hdgf-inhibits-the-tumorigenesis-of-bladder-cancer-ce-peer-reviewed-article-CMAR

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 Xu11Department 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 ChinaCorrespondence: Dawei LiDepartment of Urology, Qilu Hospital of Shandong University, Wenhuaxi Road 107#, Jinan 250012, People’s Republic of ChinaTel [phone]Fax [phone]Email [e-mail]: 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