Ubiquitin‑specific protease 22‑induced autophagy is correlated with poor prognosis of pancreatic cancer

Liang,Jin‑Xiao; Ning,Zhen; Gao,Wei; Ling,Jun; Wang,A‑Man; Luo,Hai‑Feng; Liang,Yong; Yan,Qiu; Wang,Zhong‑Yu

doi:10.3892/or.2014.3508

Ubiquitin‑specific protease 22‑induced autophagy is correlated with poor prognosis of pancreatic cancer

Authors:
- Jin‑Xiao Liang
- Zhen Ning
- Wei Gao
- Jun Ling
- A‑Man Wang
- Hai‑Feng Luo
- Yong Liang
- Qiu Yan
- Zhong‑Yu Wang
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Affiliations: Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, P.R. China, Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian, Liaoning 116011, P.R. China, Department of Basic Sciences, The Commonwealth Medical College, Scranton, PA 18509, USA, Department of Clinical Medicine, Taizhou University Medical School, Taizhou, Zhejiang 318000, P.R. China
Published online on: September 22, 2014 https://doi.org/10.3892/or.2014.3508
Pages: 2726-2734

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Abstract

Ubiquitin‑specific protease 22 (USP22) is a component of the transcription regulatory histone acetylation complex SAGA, which broadly regulates gene transcription and correlates with cancer progression, metastasis and prognosis. Autophagy is a cell pathway with dual functions that promotes cell survival or death. However, it is not known whether USP22 can regulate autophagy in pancreatic cancer. In the present study, we first identified that USP22 was overexpressed in a large number of pancreatic cancer patient samples, concomitant with the increased expression of LC3, a marker of autophagy. Statistical analysis revealed that the increase in USP22 and autophagy was positively correlated with poor prognosis of pancreatic cancer patients. Further investigation using a human pancreatic cancer cell (Panc‑1) identified that the overexpression of USP22 increased the processing of LC3 into the active form LC3‑II and the number of autophagosomes, thus leading to enhanced autophagy. Activation of ERK1/2 kinase rather than AKT1 by USP22 was found to be one of the mechanisms promoting LC3 processing. USP22‑induced autophagy was also found to enhance cell proliferation and resistance to starvation and chemotherapeutic drugs in Panc‑1 cells, therefore expressing an overall effect that promotes cell survival. Collectively, the present study demonstrated a new function of USP22 that induces autophagy, thus leading to the poor prognosis of pancreatic cancer.

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