Risk signature identification and NPRL2 affects sunitinib sensitivity in clear cell renal cell carcinoma

作者全名："Du, Xiaoyi; Zhao, Zhipeng; Zhao, Xin; Wang, Hexi; Jiang, Li; Tang, Wei"

作者地址："[Du, Xiaoyi; Zhao, Zhipeng; Wang, Hexi; Jiang, Li; Tang, Wei] Chongqing Med Univ, Affiliated Hosp 1, Dept Urol, Chongqing, Peoples R China; [Zhao, Xin] Southwest Med Univ, Affiliated Hosp, Dept Urol, Luzhou, Sichuan, Peoples R China; [Jiang, Li; Tang, Wei] 1 Youyi Rd, Chongqing 400010, Peoples R China"

通信作者："Jiang, L; Tang, W (通讯作者)，1 Youyi Rd, Chongqing 400010, Peoples R China."

来源：BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000989225100001

JCR分区：Q3

影响因子：2.5

年份：2023

卷号：663

期号：　

开始页：122

结束页：131

文献类型：Article

关键词：Tumor suppressor genes; Clear cell renal cell carcinoma; Prognostic signature; NPRL2; Sunitinib

摘要："Tumor suppressor genes (TSGs) play a crucial role in tumorigenesis and drug resistance. We analyzed the subtypes of clear cell renal cell carcinoma (ccRCC) mediated by 8 genes contained in the 3p21.3 tumor suppressor gene cluster and their effects on TME cell infiltration based on the TCGA database. The risk score model was established by principal component analysis. The hub gene NPRL2 was selected by protein-protein interactions (PPI) analysis. The effect of NPRL2 on sunitinib sensitivity of ccRCC was verified by using CCK-8, colony formation assay, wound healing assay, transwell assay and xenograft tumor model. Changes in protein expression were detected by Western blotting. We found that 8 TSGs were all differentially expressed in ccRCC samples, which could divide ccRCC into two subtypes. The constructed risk score model could predict the prognosis and drug sensitivity of ccRCC patients, and was an independent prognostic factor for ccRCC. Over-expression of NPRL2 promoted apoptosis, inhibited EMT, decreased the phosphorylation of the PI3K/AKT/mTOR signaling pathway to inhibit its activity, and promoted the sensitivity of sunitinib to ccRCC cells. Collectively, our findings increased the under-standing of TSGs in ccRCC, suggesting that NPRL2 as a TSG could enhance sunitinib sensitivity to ccRCC cells.(c) 2023 Elsevier Inc. All rights reserved."

基金机构："Natural Science Foundation of Chongqing, China [cstc2019jcyj-msxmX0708]"

基金资助正文："Funding This work was supported by the Natural Science Foundation of Chongqing, China (cstc2019jcyj-msxmX0708) ."