J Cancer 2020; 11(23):6802-6811. doi:10.7150/jca.48536

Research Paper

Ubiquitin specific peptidase 5 enhances STAT3 signaling and promotes migration and invasion in Pancreatic Cancer

Jie Lian1,2*, Chao Liu1,2*, Xin Guan1,2, Bojun Wang1,2, Yuanfei Yao1,2, Dan Su1, Yue ma1, Lin Fang1,2, Yanqiao Zhang1,2✉

1. Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang Province, China.
2. Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, Heilongjiang Province, China.
*These authors contributed equally to this work.

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Lian J, Liu C, Guan X, Wang B, Yao Y, Su D, ma Y, Fang L, Zhang Y. Ubiquitin specific peptidase 5 enhances STAT3 signaling and promotes migration and invasion in Pancreatic Cancer. J Cancer 2020; 11(23):6802-6811. doi:10.7150/jca.48536. Available from http://www.jcancer.org/v11p6802.htm

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Purpose: Ubiquitin specific peptidase 5 (USP5) has been reported to promote the progression of several malignant tumors. It may affect cancer development via modulating cell cycle and colony formation. In pancreatic cancer, the biological function of USP5, especially in migration and invasion remains unclear.

Methods: USP5 protein expression levels in primary pancreatic cancer and lymph node metastasis tissues were detected using immunohistochemistry (IHC). χ2 test, Kaplan-Meier analysis, univariate and multivariate analyses were used to evaluate the relationship between USP5 expression and clinicopathological feature. RT-qPCR were carried out to quantitate the mRNA expression levels of USP5 in pancreatic cancer cell lines. CCK8 and Colony formation assay were performed to prove how USP5 works in proliferation. Evaluation of tumor metastasis was made by Transwell and wound healing assay. EMT and STAT3 signaling related markers were detected by western blot.

Results: (1) USP5 protein expression levels were related to tumor differentiation, CEA and CA19-9 level. (2) Univariate and multivariate analyses showed that high USP5 expression is an unfavorable prognostic factor for pancreatic cancer. Kaplan-Meier analysis directly indicated that patients with high USP5 expression had shorter overall survival. (3) Increased USP5 expression is related to pancreatic cancer in both proliferation and metastasis. (4) USP5 was proved to mediate STAT3 signaling in pancreatic cancer cells.

Conclusions: The results suggest that USP5 is highly expressed and might have clinical significance for pancreatic cancer patients. High USP5 expression promotes both progression and metastasis by activating STAT3 signaling. Thus, USP5 might be a potential target in pancreatic cancer treatment.

Keywords: USP5, proliferation, metastasis, pancreatic cancer, deubiquitination, STAT3 signaling