PTPN3 suppresses the proliferation and correlates with favorable prognosis of perihilar cholangiocarcinoma by inhibiting AKT phosphorylation
Background: Perihilar cholangiocarcinoma (PHCCA) is the most common type of human cholangiocarcinoma with a very dismal prognosis. Tumor markers and target drugs of PHCCA are desperately needed. Protein phosphatase N3 (PTPN3) has dual roles in the progression of human cancers, but its expression and...
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doaj-48670378798b47c58f963200c4f8d34d2021-05-20T07:39:21ZengElsevierBiomedicine & Pharmacotherapy0753-33222020-01-01121109583PTPN3 suppresses the proliferation and correlates with favorable prognosis of perihilar cholangiocarcinoma by inhibiting AKT phosphorylationRongqi Sun0Tianli Chen1Meng Li2Zengli Liu3Bo Qiu4Zhipeng Li5Yunfei Xu6Chang Pan7Zongli Zhang8Department of General Surgery, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of General Surgery, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, ChinaDepartment of General Surgery, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of General Surgery, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of General Surgery, Shandong Provincial Hospital, Jinan, ChinaDepartment of General Surgery, Qilu Hospital of Shandong University, Jinan, ChinaDepartment of Emergency Medicine and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, China; Corresponding author at: Department of Emergency Medicine and Chest Pain Center, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, Shandong, 250012, China.Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China; Corresponding author at: Department of General Surgery, Qilu Hospital of Shandong University, 107 Wenhuaxi Road, Jinan, Shandong, 250012, China.Background: Perihilar cholangiocarcinoma (PHCCA) is the most common type of human cholangiocarcinoma with a very dismal prognosis. Tumor markers and target drugs of PHCCA are desperately needed. Protein phosphatase N3 (PTPN3) has dual roles in the progression of human cancers, but its expression and functions in PHCCA have not been elucidated. Materials and methods: The expression of PTPN3 in PHCCA was detected with western blotting, qRT-PCR and immunohistochemistry. The clinical significance of PTPN3 was identified by analyzing the correlations between its expression and the clinicopathological variables, and the prognostic value was evaluated by univariate and multivariate analyses. The functions of PTPN3 in the progression of PHCCA were estimated with both in vitro and in vivo experiments. Results: PTPN3 expression was down-regulated in PHCCA compared with normal bile duct. Low PTPN3 expression was markedly associated with large tumor size and unfavorable prognosis. After knocking down PTPN3, the percentages of G2/S phase of PHCCA cells were elevated, and the proliferation increased significantly. Moreover, we demonstrated that the phosphorylation of AKT was elevated by PTPN3 knockdown, and it was required in PTPN3-involved proliferation of PHCCA. Within vivo experiments, PTPN3 and AKT inhibitor MK-2206 were demonstrated to suppress tumor size of PHCCA. Conclusion: PTPN3 was a favorable prognostic biomarker of PHCCA. PTPN3 suppressed the proliferation of PHCCA by inhibiting AKT phosphorylation and arresting cell cycle. Our results suggested thatpost-operative detection of PTPN3 would be a helpful approach to stratify the PHCCA patients with high-risk.http://www.sciencedirect.com/science/article/pii/S0753332219352059PTPN3Perihilar cholangiocarcinomaPrognosisProliferationAKT |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rongqi Sun Tianli Chen Meng Li Zengli Liu Bo Qiu Zhipeng Li Yunfei Xu Chang Pan Zongli Zhang |
spellingShingle |
Rongqi Sun Tianli Chen Meng Li Zengli Liu Bo Qiu Zhipeng Li Yunfei Xu Chang Pan Zongli Zhang PTPN3 suppresses the proliferation and correlates with favorable prognosis of perihilar cholangiocarcinoma by inhibiting AKT phosphorylation Biomedicine & Pharmacotherapy PTPN3 Perihilar cholangiocarcinoma Prognosis Proliferation AKT |
author_facet |
Rongqi Sun Tianli Chen Meng Li Zengli Liu Bo Qiu Zhipeng Li Yunfei Xu Chang Pan Zongli Zhang |
author_sort |
Rongqi Sun |
title |
PTPN3 suppresses the proliferation and correlates with favorable prognosis of perihilar cholangiocarcinoma by inhibiting AKT phosphorylation |
title_short |
PTPN3 suppresses the proliferation and correlates with favorable prognosis of perihilar cholangiocarcinoma by inhibiting AKT phosphorylation |
title_full |
PTPN3 suppresses the proliferation and correlates with favorable prognosis of perihilar cholangiocarcinoma by inhibiting AKT phosphorylation |
title_fullStr |
PTPN3 suppresses the proliferation and correlates with favorable prognosis of perihilar cholangiocarcinoma by inhibiting AKT phosphorylation |
title_full_unstemmed |
PTPN3 suppresses the proliferation and correlates with favorable prognosis of perihilar cholangiocarcinoma by inhibiting AKT phosphorylation |
title_sort |
ptpn3 suppresses the proliferation and correlates with favorable prognosis of perihilar cholangiocarcinoma by inhibiting akt phosphorylation |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2020-01-01 |
description |
Background: Perihilar cholangiocarcinoma (PHCCA) is the most common type of human cholangiocarcinoma with a very dismal prognosis. Tumor markers and target drugs of PHCCA are desperately needed. Protein phosphatase N3 (PTPN3) has dual roles in the progression of human cancers, but its expression and functions in PHCCA have not been elucidated. Materials and methods: The expression of PTPN3 in PHCCA was detected with western blotting, qRT-PCR and immunohistochemistry. The clinical significance of PTPN3 was identified by analyzing the correlations between its expression and the clinicopathological variables, and the prognostic value was evaluated by univariate and multivariate analyses. The functions of PTPN3 in the progression of PHCCA were estimated with both in vitro and in vivo experiments. Results: PTPN3 expression was down-regulated in PHCCA compared with normal bile duct. Low PTPN3 expression was markedly associated with large tumor size and unfavorable prognosis. After knocking down PTPN3, the percentages of G2/S phase of PHCCA cells were elevated, and the proliferation increased significantly. Moreover, we demonstrated that the phosphorylation of AKT was elevated by PTPN3 knockdown, and it was required in PTPN3-involved proliferation of PHCCA. Within vivo experiments, PTPN3 and AKT inhibitor MK-2206 were demonstrated to suppress tumor size of PHCCA. Conclusion: PTPN3 was a favorable prognostic biomarker of PHCCA. PTPN3 suppressed the proliferation of PHCCA by inhibiting AKT phosphorylation and arresting cell cycle. Our results suggested thatpost-operative detection of PTPN3 would be a helpful approach to stratify the PHCCA patients with high-risk. |
topic |
PTPN3 Perihilar cholangiocarcinoma Prognosis Proliferation AKT |
url |
http://www.sciencedirect.com/science/article/pii/S0753332219352059 |
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