Oncogenic Activities Of UBE2S Mediated By VHL/HIF-1α/STAT3 Signal Via The Ubiquitin-Proteasome System In PDAC

被引：30
作者：
Wang, Lei [1 ]
Liang, Yiyi [2 ]
Li, Pengping [3 ]
Liang, Qingchun [4 ]
Sun, Haijun [5 ]
Xu, Dazhou [6 ]
Hu, Wei [7 ]
机构：
[1] Nanjing Med Univ, Peoples Hosp Lianyungang 1, Lianyungang Clin Coll, Dept Oncol, Lianyungang 222000, Jiangsu, Peoples R China
[2] Shanghai Jiao Tong Univ, Sch Med, Shanghai Canc Inst,Renji Hosp, Dept Oncol,State Key Lab Oncogenes & Related Gene, Shanghai 200127, Peoples R China
[3] Nanjing Med Univ, Sch Basic Med Sci, Dept Bioinformat, Nanjing 210029, Jiangsu, Peoples R China
[4] Cent South Univ, Xiangya Hosp 2, Dept Pathol, Changsha 410000, Hunan, Peoples R China
[5] Nanjing Med Univ, Peoples Hosp Lianyungang 1, Dept Thorac Surg, Lianyungang Clin Coll, Lianyungang 222000, Jiangsu, Peoples R China
[6] Nanjing Med Univ, Peoples Hosp Lianyungang 1, Dept Gastroenterol, Lianyungang Clin Coll, Lianyungang 222000, Jiangsu, Peoples R China
[7] Nanjing Med Univ, Peoples Hosp Lianyungang 1, Dept Hepatobiliary Surg, Lianyungang Clin Coll, Lianyungang 222000, Jiangsu, Peoples R China
来源：
ONCOTARGETS AND THERAPY | 2019年 / 12卷
基金：
中国国家自然科学基金;
关键词：
pancreatic cancer; UBE2S; VHL/HIF-1; alpha/STAT3; signaling; the ubiquitin-proteasome system; EMT; CANCER; PROTEIN; CELLS; TUMOR; APC/C; DEGRADATION; TRANSITIONS; SUPPRESSOR; E2-EPF; TARGET;
D O I：
10.2147/OTT.S228522
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
Purpose: Ubiquitin-conjugating enzyme E2S (UBE2S) is important for the development and progression of several types of cancer. However, neither the role of UBE2S in pancreatic cancer nor its mechanism is clear. Methods: We analyzed three GEO datasets to obtain 150 differentially expressed genes (DEGs) between pancreatic ductal adenocarcinoma (PDAC) and non-cancerous samples. Moreover, GSEA and mutation analysis were also done for UBE2S. The UBE2S expression in PDAC was measured by immunohistochemistry and qRT-PCR. Colony formation, scratch wound-healing and tumor growth assays were conducted to examine the effect of UBE2S on PDAC cells. Migration was detected using Transwell assay. UBE2S knockdown pancreatic cells were treated with proteasome inhibitor MG132. Immunofluorescence was undertaken for interaction between UBE2S and VHL. The expression of Snail and Twist 1 and the changes of HIF-1 alpha/STAT3 pathway were detected by Western blotting. Results: The mRNA of UBE2S was significantly upregulated in human pancreatic cancer compared to normal tissues Immunohistochemistry confirmed that the protein level of UBE2S increased in tissue microarrays (TMAs) and was associated with lymph nodes metastasis and distant metastasis. Conclusion: UBE2S could enhance EMT by the VHL/HIF-1 alpha/STAT3 pathway via the ubiquitin-proteasome system. Co-expression of CDC20 may represent a novel and promising therapeutic target for the patients with PDAC.
引用
收藏
页码：9767 / 9781
页数：15
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