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Neurotrophin3 promotes hepatocellular carcinoma apoptosis through the JNK and P38 MAPK pathways
Although liver cancer is a malignant tumor with the highest mortality across the world, its pathogenesis and therapeutic targets remain unclear. Apoptosis, a natural cell death mechanism, is an important target of anticancer therapy. The discovery of effective apoptotic regulators can lead to the id...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576519/ https://www.ncbi.nlm.nih.gov/pubmed/36263167 http://dx.doi.org/10.7150/ijbs.72982 |
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author | Yang, Zhangshuo Zhang, Hao Yin, Maohui Cheng, Zhixiang Jiang, Ping Feng, Maohui Liao, Bo Liu, Zhisu |
author_facet | Yang, Zhangshuo Zhang, Hao Yin, Maohui Cheng, Zhixiang Jiang, Ping Feng, Maohui Liao, Bo Liu, Zhisu |
author_sort | Yang, Zhangshuo |
collection | PubMed |
description | Although liver cancer is a malignant tumor with the highest mortality across the world, its pathogenesis and therapeutic targets remain unclear. Apoptosis, a natural cell death mechanism, is an important target of anticancer therapy. The discovery of effective apoptotic regulators can lead to the identification of novel therapeutic targets for treating cancer. Neurotrophin 3 (NTF3) is a member of the nerve growth factor (NGF) family that is involved in the progression of various cancers, including medulloblastoma, primitive neuroectodermal brain tumors, and breast cancer. NTF3 is under-expressed in human hepatocellular carcinoma (HCC), albeit its specific effects and the action mechanism have not been elucidated. Here, we confirmed that NTF3 expression was significantly low in HCC with reference to the GSEA database. By collecting patient data from our center and performing qRT-PCR analysis, we found that NTF3 expression was significantly downregulated in 74 patients with HCC. Low NTF3 expression was associated with a shorter overall survival (OS), recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). Both in vivo and in vitro experiments revealed that NTF3 considerably inhibited the progression of HCC cells. We found that the ligand NTF3 is regulated by c-Jun and binds to the p75 neurotrophin receptor (p75NTR) and then activates the JNK and P38 MAPK pathways to induce apoptosis. Entinostat (the target of HDAC1/HDAC3) can activate the NTF3/p75NTR pathway. These results indicate that NTF3 is a tumor suppressor, and that its low expression can help in predict poor clinical outcomes in HCC. Therefore, NTF3 can be used as a potential treatment molecule for HCC. |
format | Online Article Text |
id | pubmed-9576519 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Ivyspring International Publisher |
record_format | MEDLINE/PubMed |
spelling | pubmed-95765192022-10-18 Neurotrophin3 promotes hepatocellular carcinoma apoptosis through the JNK and P38 MAPK pathways Yang, Zhangshuo Zhang, Hao Yin, Maohui Cheng, Zhixiang Jiang, Ping Feng, Maohui Liao, Bo Liu, Zhisu Int J Biol Sci Research Paper Although liver cancer is a malignant tumor with the highest mortality across the world, its pathogenesis and therapeutic targets remain unclear. Apoptosis, a natural cell death mechanism, is an important target of anticancer therapy. The discovery of effective apoptotic regulators can lead to the identification of novel therapeutic targets for treating cancer. Neurotrophin 3 (NTF3) is a member of the nerve growth factor (NGF) family that is involved in the progression of various cancers, including medulloblastoma, primitive neuroectodermal brain tumors, and breast cancer. NTF3 is under-expressed in human hepatocellular carcinoma (HCC), albeit its specific effects and the action mechanism have not been elucidated. Here, we confirmed that NTF3 expression was significantly low in HCC with reference to the GSEA database. By collecting patient data from our center and performing qRT-PCR analysis, we found that NTF3 expression was significantly downregulated in 74 patients with HCC. Low NTF3 expression was associated with a shorter overall survival (OS), recurrence-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). Both in vivo and in vitro experiments revealed that NTF3 considerably inhibited the progression of HCC cells. We found that the ligand NTF3 is regulated by c-Jun and binds to the p75 neurotrophin receptor (p75NTR) and then activates the JNK and P38 MAPK pathways to induce apoptosis. Entinostat (the target of HDAC1/HDAC3) can activate the NTF3/p75NTR pathway. These results indicate that NTF3 is a tumor suppressor, and that its low expression can help in predict poor clinical outcomes in HCC. Therefore, NTF3 can be used as a potential treatment molecule for HCC. Ivyspring International Publisher 2022-10-03 /pmc/articles/PMC9576519/ /pubmed/36263167 http://dx.doi.org/10.7150/ijbs.72982 Text en © The author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions. |
spellingShingle | Research Paper Yang, Zhangshuo Zhang, Hao Yin, Maohui Cheng, Zhixiang Jiang, Ping Feng, Maohui Liao, Bo Liu, Zhisu Neurotrophin3 promotes hepatocellular carcinoma apoptosis through the JNK and P38 MAPK pathways |
title | Neurotrophin3 promotes hepatocellular carcinoma apoptosis through the JNK and P38 MAPK pathways |
title_full | Neurotrophin3 promotes hepatocellular carcinoma apoptosis through the JNK and P38 MAPK pathways |
title_fullStr | Neurotrophin3 promotes hepatocellular carcinoma apoptosis through the JNK and P38 MAPK pathways |
title_full_unstemmed | Neurotrophin3 promotes hepatocellular carcinoma apoptosis through the JNK and P38 MAPK pathways |
title_short | Neurotrophin3 promotes hepatocellular carcinoma apoptosis through the JNK and P38 MAPK pathways |
title_sort | neurotrophin3 promotes hepatocellular carcinoma apoptosis through the jnk and p38 mapk pathways |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9576519/ https://www.ncbi.nlm.nih.gov/pubmed/36263167 http://dx.doi.org/10.7150/ijbs.72982 |
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