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NSD2 Promotes Renal Cancer Progression Through Stimulating Akt/Erk Signaling
Xu Han1, Lianhua Piao2, Xiaoshuang Xu2
1Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou 213003, People's Republic of China.
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.
Insights
Nuclear receptor SET domain-containing 2 (NSD2) is overexpressed in clear cell renal cell carcinoma (ccRCC), promoting cancer progression by activating Akt/Erk signaling. NSD2 inhibition suppressed tumor growth and improved survival in ccRCC models.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Nuclear receptor SET domain-containing 2 (NSD2) is a histone lysine methyltransferase.
- The role of NSD2 in clear cell renal cell carcinoma (ccRCC) requires further investigation.
Purpose of the Study:
- To investigate the biological role and clinical significance of NSD2 in ccRCC.
- To elucidate the underlying molecular mechanisms by which NSD2 influences ccRCC progression.
Main Methods:
- Bioinformatic analysis of NSD2 expression in ccRCC using GEO and OncoLnc databases.
- Immunohistochemistry (IHC) to assess NSD2 protein levels in ccRCC tissues.
- In vitro (cell lines) and in vivo (xenograft) assays to evaluate the functional impact of NSD2 modulation on ccRCC progression, including proliferation, apoptosis, and signaling pathways (Akt/Erk).
Main Results:
- NSD2 is significantly overexpressed in ccRCC tissues and cell lines, distinguishing ccRCC from normal samples.
- High NSD2 expression correlates with shorter overall survival (OS) in ccRCC patients.
- NSD2 knockdown inhibits ccRCC cell proliferation, induces apoptosis by downregulating Bcl-2 and upregulating Bax, and suppresses tumor growth in vivo, mediated by Akt/Erk signaling inhibition.
Conclusions:
- NSD2 acts as an oncogenic factor in ccRCC progression.
- Activation of Akt/Erk signaling by NSD2 is a key mechanism driving ccRCC.
- Targeting NSD2 may represent a potential therapeutic strategy for ccRCC.
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