title: Proteasome activator subunit 3 promotes pancreatic cancer growth via c-Myc-glycolysis signaling axis.
abstract: Pancreatic cancer has the worst prognosis among all cancers and novel markers and therapeutic targets are desperately needed for this terribly deadly disease. Proteasome activator subunit 3 (PSME3) is highly involved in the initiation and progression of many human cancers. However, the potential effect of PSME3 on pancreatic cancer remains largely unknown. In the present study, we first found that PSME3 was significantly upregulated in pancreatic cancer cells and tissues at both mRNA and protein levels using qRT-PCR, western blot analysis, Oncomine data mining and immunohistochemical analysis. High PSME3 expression was positively correlated with tumor size and pM stage, and was significantly correlated with poor prognosis in pancreatic cancer patients revealed by Kaplan-Meier analysis. Gene set enrichment analysis demonstrated that the gene sets related to cell proliferation and metastasis were positively correlated with elevated PSME3 expression. Consistently, silencing of PSME3 suppressed cell proliferation and invasive capacity of pancreatic cancer. Mechanistically, PSME3 inhibited the degradation of c-Myc and thus enhanced glycolysis, which ultimately led to the oncogenic effects of PSME3 on pancreatic cancer. Collectively, our data suggest that PSME3 plays oncogenic roles in pancreatic cancer by inhibiting c-Myc degradation to promote glycolysis, and could serve as a novel therapeutic target for pancreatic cancer treatment.
authors.affiliation: Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jiefang
authors.initials: J
authors.lastname: Guo
authors.affiliation: Department of Pancreatic Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hao
authors.affiliation: Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hongxue
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. Electronic address: zhendjin@126.com.
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Jin
authors.affiliation: Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. Electronic address: lizhaoshen111@gmail.com.
authors.forename: Zhaoshen
authors.initials: Z
authors.lastname: Li
mesh_terms: D000368:Aged; D001324:Autoantigens / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D006019:Glycolysis; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D055550:Protein Stability; D059748:Proteolysis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden
chemical_list: D001324:Autoantigens; C099558:Ki antigen; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D046988:Proteasome Endopeptidase Complex
keywords: Glycolysis; PSME3; Pancreatic cancer; c-Myc