Int J Med Sci 2019; 16(10):1404-1411. doi:10.7150/ijms.36128
Knockdown of NSD2 Suppresses Renal Cell Carcinoma Metastasis by Inhibiting Epithelial-Mesenchymal Transition
1. Department of Urology, The Third Affiliated Hospital of Soochow University, 213003, Changzhou, China
2. Institute of Bioinformatics and Medical Engineering, Jiangsu University of Technology, 213001, Changzhou, China
3. Department of Orthopaedics, The Third Affiliated Hospital of Soochow University, 213003, Changzhou, China
* The authors contributed equally to this study.
Han X, Piao L, Yuan X, Wang L, Liu Z, He X. Knockdown of NSD2 Suppresses Renal Cell Carcinoma Metastasis by Inhibiting Epithelial-Mesenchymal Transition. Int J Med Sci 2019; 16(10):1404-1411. doi:10.7150/ijms.36128. Available from http://www.medsci.org/v16p1404.htm
Background: Renal cell carcinoma (RCC) accounts for around 85% of all primary kidney neoplasms, which is one of top 10 common cancers worldwide. Nuclear receptor suppressor of variegation, enhancer of zeste, and trithorax (SET) domain-containing 2 (NSD2), belonging to NSD protein family, functions as an oncogene in the pathogenesis of multiple cancers.
Methods: GEO database was used to analyze the expression of NSD2 mRNA in renal cancer. Furthermore, NSD2 protein level in clear cell RCC (ccRCC) tissues was detected by immunohistochemistry (IHC). Knockdown efficiency of different siRNAs was evaluated by quantitative real-time PCR (qRT-PCR) and western blot analysis. The biological role and molecular mechanism of NSD2 in RCC metastasis were investigated via a series of functional experiments.
Results: NSD2 mRNA was massively amplified in several types of renal cancer, especially in metastatic ccRCC. The expression level of NSD2 protein was elevated in ccRCC tissues, but not correlated with pathological grading. The migratory and invasive properties were significantly repressed in NSD2-silenced RCC cells, concurrent with an increase of E-cadherin expression and a decrease of N-cadherin and Vimentin expression.
Conclusion: Down-regulation of NSD2 could potently suppress cell migration and invasion through inhibiting epithelial-mesenchymal transition (EMT), indicating that NSD2 may be a potential therapeutic target for metastatic RCC.
Keywords: NSD2, renal cell carcinoma, metastasis, epithelial-mesenchymal transition