title: USP39, a direct target of microRNA-133a, promotes progression of pancreatic cancer via the AKT pathway.
abstract: Ubiquitin specific protease 39 (USP39) is one of the deubiquitinating enzymes without ubiquitin protease activity, which has been implicated in the progression of several cancers. However, the role of USP39 in pancreatic cancer (PC) is largely unknown. In present study, we found that USP39 expression was elevated in PC tissues than adjacent non-tumor tissues. Importantly, we demonstrated that overexpression of USP39 is closely correlated with tumor progression and poor survival in PC patients. Furthermore, high USP39 expression was observed in PC cell lines and ectopic expression of USP39 significantly enhanced in vitro cell proliferation and promoted in vivo tumor growth, whereas silencing USP39 suppressed growth of PC cells. Besides, our experimental data revealed that knockdown of USP39 induced cell apoptosis through inhibition of AKT signaling pathway in PC cells. Moreover, USP39 was a direct target of miR-133a, a microRNA that has been reported to be involved in progression of PC. Taken together, our data provide a novel PC regulatory axis that is miR-133a/USP39, the dysfunction of which drives diverse aspects of the progression of PC.
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Tiande
authors.initials: T
authors.lastname: Liu
authors.affiliation: School of Public Health of Nanchang University, Nanchang 330006, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Oncology, Jiangxi Provincial Cancer Hospital, Nanchang 330029, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yan
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Changkuo
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China.
authors.forename: Le
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, China. Electronic address: liuanwen168@126.com.
authors.forename: Anwen
authors.initials: A
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D014183:Transplantation, Heterologous; D064570:Ubiquitin-Specific Proteases / Q000235:genetics* / Q000378:metabolism
chemical_list: C548234:MIRN133 microRNA, human; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; C579218:USP39 protein, human; D064570:Ubiquitin-Specific Proteases
keywords: AKT pathway; Apoptosis; Pancreatic cancer; USP39; miR-133a