USP39, a direct target of microRNA-133a, promotes progression of pancreatic cancer via the AKT pathway

• Published in: Biochemical and biophysical research communications Vol. 486; no. 1; pp. 184 - 190
• Main Authors: Cai, Jing, Liu, Tiande, Huang, Peng, Yan, Wei, Guo, Changkuo, Xiong, Le, Liu, Anwen
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.04.2017
• Subjects: 60 APPLIED LIFE SCIENCES; AKT pathway; Animals; Apoptosis; Apoptosis - genetics; Blotting, Western; Cell Line; Cell Line, Tumor; CELL PROLIFERATION; Cell Proliferation - genetics; Disease Progression; EXPERIMENTAL DATA; Female; Gene Expression Regulation, Neoplastic; Humans; IN VIVO; Kaplan-Meier Estimate; Male; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; Middle Aged; miR-133a; NEOPLASMS; PANCREAS; Pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - pathology; PLANT GROWTH; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Signal Transduction - genetics; Transplantation, Heterologous; Ubiquitin-Specific Proteases - genetics; Ubiquitin-Specific Proteases - metabolism; USP39; miR-133a; USP39; Pancreatic cancer; AKT pathway; Apoptosis
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.03.025

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. •Upregulation of USP39 expression was significantly associated with the progression and poor survival in PC patients.•Overexpression of USP39 promotes PC cell growth in vitro and in vivo.•AKT pathway partly contributed to the oncogenic effects of USP39 in PC cells.•USP39 was found to be a direct target of miR-133a, which has been reported to be involved in progression of PC.