scholarly journals Posttranscriptional Inhibition of Protein Tyrosine Phosphatase Nonreceptor Type 23 by Staphylococcal Nuclease and Tudor Domain Containing 1: Implications for Hepatocellular Carcinoma

2019 ◽  
Vol 3 (9) ◽  
pp. 1258-1270 ◽  
Author(s):  
Nidhi Jariwala ◽  
Rachel G. Mendoza ◽  
Dawn Garcia ◽  
Zhao Lai ◽  
Mark A. Subler ◽  
...  
2020 ◽  
Vol 8 (1) ◽  
pp. e000285 ◽  
Author(s):  
Wenjie Zhang ◽  
Yang Liu ◽  
Zhongyi Yan ◽  
Hui Yang ◽  
Wei Sun ◽  
...  

BackgroundWe have previously discovered a relationship between the low expression of protein tyrosine phosphatase, receptor type O (PTPRO) in tumor-infiltrating T cells and immunosuppression. The aim of the present study was to investigate the relationship between decreased PTPRO and increased programmed death ligand 1 (PD-L1) in both the peripheral monocytes and tumor-infiltrating macrophages of human hepatocellular carcinoma (HCC).MethodsThe expression and correlation of all the indices were explored in monocytes and tumor-infiltrating macrophages within both human and mice HCC. The mechanic regulations were studied by using both in vitro and in vivo studies.ResultsWe found a significant decrease in PTPRO in HCC peripheral monocytes that was associated with increased PD-L1 expression in peripheral monocytes and tumor-associated macrophages (TAMs) in HCC. Monocyte PD-L1 and PTPRO therefore could serve as valuable prognostic indicators for post-surgery patients with HCC and were associated with increased T-cell exhaustion (Tim3+T cells). A depletion of PTPRO promoted PD-L1 secretion in both monocytes and macrophages through the JAK2/STAT1 and JAK2/STAT3/c-MYC pathways. Increased IL-6 expression was associated with activation of JAK2/STAT3/c-MYC and with decreased PTPRO expression through the STAT3/c-MYC/miR-25–3 p axis. Monocytes and TAMs showed significantly increased miR-25–3 p expression, which could target the 3′ untranslated region of PTPRO. The miR-25–3 p expression positively correlated with serum IL-6 levels, but inversely correlated with PTPRO in HCC monocytes. IL-6/STAT3/c-MYC activation enhanced in vitro miR-25–3 p transcription and decreased PTPRO, while further promoting PD-L1 secretion. Adoptive cell transfer of c-MYC/miR-25–3 p–modified monocytes promoted tumor growth by downregulating PTPRO and causing a PD-L1–induced immunosuppression in an orthotopic tumor transplantation model.ConclusionsIncreased serum IL-6 downregulated PTPRO expression in HCC monocytes and macrophages by activating STAT3/c-MYC/miR-25–3 p and by further enhancing PD-L1 expression through JAK2/STAT1 and JAK2/STAT3/c-MYC signaling.


Oncogene ◽  
2003 ◽  
Vol 22 (30) ◽  
pp. 4656-4663 ◽  
Author(s):  
Hidenobu Nagano ◽  
Tetsuya Noguchi ◽  
Kenjiro Inagaki ◽  
Seitetsu Yoon ◽  
Takashi Matozaki ◽  
...  

Hepatology ◽  
2016 ◽  
Vol 63 (5) ◽  
pp. 1528-1543 ◽  
Author(s):  
Wei-Tien Tai ◽  
Yao-Li Chen ◽  
Pei-Yi Chu ◽  
Li-Ju Chen ◽  
Man-Hsin Hung ◽  
...  

2021 ◽  
Vol 5 (2) ◽  
Author(s):  
Ye Qin ◽  
Xinke Xie

Pathologist Virchow has proposed a hypothesis that the origin of tumors comes from chronic inflammation. Clinically, liver tumors can be divided into three types Hepatocellular carcinoma (HCC) is the most common type, which is closely related to various kinds of inflammation. Studies have shown that protein tyrosine phosphatase receptor type O (PTPRO) is a new type of protein tyrosine phosphatase, which is negatively correlated with tumorigenesis. As a new tumor suppressor protein, PTPRO is of great significance for the diagnosis and treatment of HCC in the future. This paper aims to discuss the mechanism of PTPRO in HCC.


2021 ◽  
Vol 5 (6) ◽  
pp. 94-97
Author(s):  
Xiangzhe Yang ◽  
Ye Qin ◽  
Xinke Xie

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in the world with a high incidence and has become one of the most malignant cancers worldwide. Its clinical treatment mainly includes surgical intervention, chemotherapy, and immunotherapy, with poor curative effect and prognosis. In recent years, with the development of basic research, it has been revealed that protein tyrosine phosphatase receptor-type O (PTPRO) plays an important role in the pathogenesis of hepatocellular carcinoma. Protein tyrosine phosphatase receptor-type O is a new type of protein tyrosine phosphatase, which has been proven to inhibit oncoprotein. In this paper, the potential mechanism of protein tyrosine phosphatase receptor -type O in the progression of hepatocellular carcinoma is discussed to provide reference for clinical treatment and drug development.


1994 ◽  
Vol 29 (6) ◽  
pp. 727-732 ◽  
Author(s):  
Shigeo Ikuta ◽  
Fumio Itoh ◽  
Yuji Hinoda ◽  
Minoru Toyota ◽  
Yusuke Makiguchi ◽  
...  

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