机构：[1]Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China[2]The First Affiliated Hospital, Sun Yat-sen university, Guangzhou, China中山大学附属第一医院[3]Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China广东省中医院[4]Gaozhou People’s Hospital, Gaozhou, China[5]State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China
Pancreatic cancer is one of the major malignancies and causes of mortality worldwide. E3 ubiquitin-protein ligases transfer activated ubiquitin from ubiquitin-conjugating enzymes to protein substrates and confer substrate specificity in cancer. In this study, we first downloaded data from The Cancer Genome Atlas pancreatic adenocarcinoma dataset, acquired all 27 differentially expressed genes (DEGs), and identified genomic alterations. Then, the prognostic significance of DEGs was analyzed, and eight DEGs (MECOM, CBLC, MARCHF4, RNF166, TRIM46, LONRF3, RNF39, and RNF223) and two clinical parameters (pathological N stage and T stage) exhibited prognostic significance. RNF223 showed independent significance as an unfavorable prognostic marker and was chosen for subsequent analysis. Next, the function of RNF223 in the pancreatic cancer cell lines ASPC-1 and PANC-1 was investigated, and RNF223 silencing promoted pancreatic cancer growth and migration. To explore the potential targets and pathways of RNF223 in pancreatic cancer, quantitative proteomics was applied to analyze differentially expressed proteins, and metabolism-related pathways were primarily enriched. Finally, the reason for the elevated expression of RNF223 was analyzed, and KLF4 was shown to contribute to the increased expression of RNF233. In conclusion, this study comprehensively analyzed the clinical significance of E3 ligases. Functional assays revealed that RNF223 promotes cancer by regulating cell metabolism. Finally, the elevated expression of RNF223 was attributed to KLF4-mediated transcriptional activation. This study broadens our knowledge regarding E3 ubiquitin ligases and signal transduction and provides novel markers and therapeutic targets in pancreatic cancer.</p>
基金：
National Key R&D Program of China [2018YFC1106400]; Guangdong Basic and Applied Basic Research Foundation [2020A1515111111]; Beijing iGandan Foundation [RGGJJ-2021-008]
第一作者机构：[1]Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China
共同第一作者：
通讯作者：
通讯机构：[1]Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, China[5]State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, China
推荐引用方式(GB/T 7714)：
Feng Lei,Wang Jieqing,Zhang Jianmin,et al.Comprehensive Analysis of E3 Ubiquitin Ligases Reveals Ring Finger Protein 223 as a Novel Oncogene Activated by KLF4 in Pancreatic Cancer[J].FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY.2021,9:doi:10.3389/fcell.2021.738709.
APA：
Feng, Lei,Wang, Jieqing,Zhang, Jianmin,Diao, Jingfang,He, Longguang...&Zhou, Chenjie.(2021).Comprehensive Analysis of E3 Ubiquitin Ligases Reveals Ring Finger Protein 223 as a Novel Oncogene Activated by KLF4 in Pancreatic Cancer.FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY,9,
MLA：
Feng, Lei,et al."Comprehensive Analysis of E3 Ubiquitin Ligases Reveals Ring Finger Protein 223 as a Novel Oncogene Activated by KLF4 in Pancreatic Cancer".FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY 9.(2021)
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