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Aberrant expression of NPPB through YAP1 and TAZ activation in mesothelioma with Hippo pathway gene alterations
BACKGROUND: Mesothelioma is a neoplastic disease associated with asbestos exposure. It is highly malignant and has a poor prognosis; thus, early detection is desirable. Recent whole‐genome analysis has revealed that mesothelioma is characterized by a high frequency of mutations in a set of genes inv...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10315720/ https://www.ncbi.nlm.nih.gov/pubmed/37165917 http://dx.doi.org/10.1002/cam4.6056 |
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author | Sato, Tatsuhiro Akao, Ken Sato, Ayuko Tsujimura, Tohru Mukai, Satomi Sekido, Yoshitaka |
author_facet | Sato, Tatsuhiro Akao, Ken Sato, Ayuko Tsujimura, Tohru Mukai, Satomi Sekido, Yoshitaka |
author_sort | Sato, Tatsuhiro |
collection | PubMed |
description | BACKGROUND: Mesothelioma is a neoplastic disease associated with asbestos exposure. It is highly malignant and has a poor prognosis; thus, early detection is desirable. Recent whole‐genome analysis has revealed that mesothelioma is characterized by a high frequency of mutations in a set of genes involved in the Hippo pathway, such as NF2 and LATS2. However, a rapid, simple, and precise method for finding mesothelioma with these mutations has not yet been established. METHODS: Clustering of Hippo pathway gene alteration groups and the differential expression of each gene in mesothelioma patients were analyzed using The Cancer Genome Atlas database. Gene expression levels in various tumors and normal tissues were analyzed using public databases. Knockdown or transient expression of YAP1 or TAZ was performed to evaluate the regulation of gene expression by these genes. NT‐proBNP was measured in the pleural effusions of 18 patients and was compared with NF2 expression in five cases where cell lines had been successfully established. RESULTS: NPPB mRNA expression was markedly higher in the group of mesothelioma patients with Hippo pathway gene mutations than in the group without them. NPPB expression was low in all normal tissues except heart, and was highest in mesothelioma. Mesothelioma patients in the high NPPB expression group had a significantly worse prognosis than those in the low NPPB expression group. NPPB expression was suppressed by knockdown of YAP1 or TAZ. NT‐proBNP was abundant in the effusions of mesothelioma patients and was particularly high in those with impaired NF2 expression. CONCLUSIONS: NPPB, whose levels can be measured in pleural effusions of mesothelioma patients, has the potential to act as a biomarker to detect NF2‐Hippo pathway gene alterations and/or predict patient prognosis. Additionally, it may provide useful molecular insights for a better understanding of mesothelioma pathogenesis and for the development of novel therapies. |
format | Online Article Text |
id | pubmed-10315720 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103157202023-07-04 Aberrant expression of NPPB through YAP1 and TAZ activation in mesothelioma with Hippo pathway gene alterations Sato, Tatsuhiro Akao, Ken Sato, Ayuko Tsujimura, Tohru Mukai, Satomi Sekido, Yoshitaka Cancer Med RESEARCH ARTICLES BACKGROUND: Mesothelioma is a neoplastic disease associated with asbestos exposure. It is highly malignant and has a poor prognosis; thus, early detection is desirable. Recent whole‐genome analysis has revealed that mesothelioma is characterized by a high frequency of mutations in a set of genes involved in the Hippo pathway, such as NF2 and LATS2. However, a rapid, simple, and precise method for finding mesothelioma with these mutations has not yet been established. METHODS: Clustering of Hippo pathway gene alteration groups and the differential expression of each gene in mesothelioma patients were analyzed using The Cancer Genome Atlas database. Gene expression levels in various tumors and normal tissues were analyzed using public databases. Knockdown or transient expression of YAP1 or TAZ was performed to evaluate the regulation of gene expression by these genes. NT‐proBNP was measured in the pleural effusions of 18 patients and was compared with NF2 expression in five cases where cell lines had been successfully established. RESULTS: NPPB mRNA expression was markedly higher in the group of mesothelioma patients with Hippo pathway gene mutations than in the group without them. NPPB expression was low in all normal tissues except heart, and was highest in mesothelioma. Mesothelioma patients in the high NPPB expression group had a significantly worse prognosis than those in the low NPPB expression group. NPPB expression was suppressed by knockdown of YAP1 or TAZ. NT‐proBNP was abundant in the effusions of mesothelioma patients and was particularly high in those with impaired NF2 expression. CONCLUSIONS: NPPB, whose levels can be measured in pleural effusions of mesothelioma patients, has the potential to act as a biomarker to detect NF2‐Hippo pathway gene alterations and/or predict patient prognosis. Additionally, it may provide useful molecular insights for a better understanding of mesothelioma pathogenesis and for the development of novel therapies. John Wiley and Sons Inc. 2023-05-11 /pmc/articles/PMC10315720/ /pubmed/37165917 http://dx.doi.org/10.1002/cam4.6056 Text en © 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | RESEARCH ARTICLES Sato, Tatsuhiro Akao, Ken Sato, Ayuko Tsujimura, Tohru Mukai, Satomi Sekido, Yoshitaka Aberrant expression of NPPB through YAP1 and TAZ activation in mesothelioma with Hippo pathway gene alterations |
title | Aberrant expression of
NPPB
through YAP1 and TAZ activation in mesothelioma with Hippo pathway gene alterations |
title_full | Aberrant expression of
NPPB
through YAP1 and TAZ activation in mesothelioma with Hippo pathway gene alterations |
title_fullStr | Aberrant expression of
NPPB
through YAP1 and TAZ activation in mesothelioma with Hippo pathway gene alterations |
title_full_unstemmed | Aberrant expression of
NPPB
through YAP1 and TAZ activation in mesothelioma with Hippo pathway gene alterations |
title_short | Aberrant expression of
NPPB
through YAP1 and TAZ activation in mesothelioma with Hippo pathway gene alterations |
title_sort | aberrant expression of
nppb
through yap1 and taz activation in mesothelioma with hippo pathway gene alterations |
topic | RESEARCH ARTICLES |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10315720/ https://www.ncbi.nlm.nih.gov/pubmed/37165917 http://dx.doi.org/10.1002/cam4.6056 |
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