单位：[1]Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China临床科室泌尿外科泌尿外科首都医科大学附属北京友谊医院[2]Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, China[3]Core Facilities Center, Capital Medical University, Beijing, China[4]Key Laboratory of Biology of Insect-Pollinator, Ministry of Agriculture, Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing, China[5]Beijing Key Laboratory for Tumor Invasion and Metastasis, Cancer Institute of Capital Medical University, Beijing, China
Background. Clear cell renal cell carcinoma (ccRCC) is the most common and lethal cancer of the adult kidney. However, its pathogenesis has not been fully understood till now, which hinders the therapeutic development of ccRCC. NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4-like 2 (NDUFA4L2) was found to be upregulated and play an important role in ccRCC. We aimed to further investigate the underlying mechanisms by which NDUFA4L2 exerted function and its expression level was upregulated.& para;& para;Methods. The Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) data were mined to verify the change of NDUFA4L2 expression level in ccRCC tissues. The correlation between expression level of NDLJFA4L2 and cell proliferation/apoptosis was explored by Gene Set Enrichment Analysis (GSEA). Protein-protein interaction (PPI) network of NDUFA4L2 was constructed. Biological process and involved pathways of NDUFA4L2 were analyzed by gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The transcription factors (TFs) which can induce the expression of NDLJFA4L2 were explored in clinical samples by correlation analysis and its regulation on the expression of NDUFA4L2 was verified by knockdown experiment.& para;& para;Results. NDUFA4L2 was verified to be overexpressed in ccRCC tissues and its expression level was increased accordingly as the American Joint Committee on Cancer (AJCC) stage progressed. A high NDUFA4L2 level predicted the poor prognosis of ccRCC patients and correlated with enhanced cell proliferation and anti-apoptosis. NDUFA4L2 may interact with 14 tumor-related proteins, participate in growth and death processes and be involved in ccRCC-related pathways, such as insulin-like growth factor 1 (IGF-1), mammalian target of Rapamycin (mTOR) and phosphoinositide 3 kinase serine/threonine protein kinase (PI3K/AKT). ETS domain-containing protein ELK1 level positively correlated with the level of NDUFA4L2 in ccRCC tissues and ELK1 could regulate the expression of NDUFA4L2 in ccRCC cells.& para;& para;Discussion. NDUFA4L2 upregulation was associated with ccRCC malignancy. ND-UFA4L2 expression was regulated by ELK1 in ccRCC cells. Our study provided potential mechanisms by which NDUFA4L2 affected ccRCC occurrence and progression.
基金：
National Natural Science Foundation of the Peopleapos;s Republic of China [81372739, 81672521]; Scientific Research Foundation of Beijing Friendship Hospital [Yyqdkt2015-14]
第一作者单位：[1]Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
共同第一作者：
通讯作者：
通讯机构：[2]Department of Biochemistry and Molecular Biology, Capital Medical University, Beijing, China[5]Beijing Key Laboratory for Tumor Invasion and Metastasis, Cancer Institute of Capital Medical University, Beijing, China
推荐引用方式(GB/T 7714)：
Wang Lei,Peng Zhiqiang,Wang Kaizhen,et al.NDUFA4L2 is associated with clear cell renal cell carcinoma malignancy and is regulated by ELK1[J].PEERJ.2017,5:doi:10.7717/peerj.4065.
APA：
Wang, Lei,Peng, Zhiqiang,Wang, Kaizhen,Qi, Yijun,Yang, Ying...&Zheng, Junfang.(2017).NDUFA4L2 is associated with clear cell renal cell carcinoma malignancy and is regulated by ELK1.PEERJ,5,
MLA：
Wang, Lei,et al."NDUFA4L2 is associated with clear cell renal cell carcinoma malignancy and is regulated by ELK1".PEERJ 5.(2017)
