NSD2 Promotes Renal Cancer Progression Through Stimulating Akt/Erk Signaling
Authors Han X, Piao L, Xu X, Luo F, Liu Z, He X
Received 16 July 2019
Accepted for publication 6 November 2019
Published 16 January 2020 Volume 2020:12 Pages 375—383
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Eileen O'Reilly
Xu Han, 1,* Lianhua Piao, 2,* Xiaoshuang Xu, 2 Fengbao Luo, 1 Zhiwei Liu, 3 Xiaozhou He 1
1Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, People’s Republic of China; 2Institute of Bioinformatics and Medical Engineering, Jiangsu University of Technology, Changzhou 213001, People’s Republic of China; 3Department of Orthopaedics, The Third Affiliated Hospital of Soochow University, Changzhou 213003, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Xiaozhou He
Department of Urology, The Third Affiliated Hospital of Soochow University, 185 Juqian Street, Changzhou 213003, Jiangsu Province, People’s Republic of China
Tel +86 519 6887 1251
Background: Nuclear receptor suppressor of variegation, enhancer of zeste, and trithorax (SET) domain-containing 2 (NSD2), is a well-known histone lysine methyltransferase (HMTase). The aim of this study was to investigate the biological role of NSD2 in clear cell renal cell carcinoma (ccRCC).
Methods: GEO and OncoLnc databases were used to identify NSD2 expression and estimate its clinical value in ccRCC. Immunohistochemistry (IHC) was applied to further evaluate NSD2 protein level in ccRCC tissues. The expression of NSD2 in different cell lines and the transfection efficiency were determined by quantitative real-time PCR and Western blot analysis. The effect of NSD2 and the underlying mechanism in ccRCC progression were investigated via MTT, flow cytometry, Western blotting and xenograft tumor assays.
Results: NSD2 was over-expressed in both ccRCC tissues and cell lines. NSD2 expression could discriminate ccRCC samples from normal samples, and moreover, high NSD2 expression was characterized with a short overall survival (OS) time. Additionally, knockdown of NSD2 suppressed proliferation and induced apoptosis of cancer cells by inhibiting Akt/Erk signaling and regulating Bcl-2 and Bax expression. Meanwhile, up-regulation of NSD2 contributed to the opposite effects. Silencing of NSD2 reduced xenograft tumor growth in vivo.
Conclusion: NSD2 serves as an oncogenic factor in the progression of ccRCC via activation of Akt/Erk signaling.
Keywords: NSD2, renal cancer, proliferation, apoptosis, Akt/Erk signaling
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