Cargando…
Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer
Breast cancer (BC) is one of the most common malignancies among women worldwide. It is necessary to search for improvement in diagnosis and treatment methods to improve the prognosis. Protein kinase, membrane associated tyrosine/threonine 1 (PKMYT1), a member of the Wee family of protein kinases, ha...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9922894/ https://www.ncbi.nlm.nih.gov/pubmed/36793346 http://dx.doi.org/10.3389/fonc.2022.1002186 |
_version_ | 1784887628653395968 |
---|---|
author | Li, Huihui Wang, Li Zhang, Wei Dong, Youting Cai, Yefeng Huang, Xiaoli Dong, Xubin |
author_facet | Li, Huihui Wang, Li Zhang, Wei Dong, Youting Cai, Yefeng Huang, Xiaoli Dong, Xubin |
author_sort | Li, Huihui |
collection | PubMed |
description | Breast cancer (BC) is one of the most common malignancies among women worldwide. It is necessary to search for improvement in diagnosis and treatment methods to improve the prognosis. Protein kinase, membrane associated tyrosine/threonine 1 (PKMYT1), a member of the Wee family of protein kinases, has been studied in some tumors except BC. This study has explored that PKMYT1 functional role by bioinformatics methods combined with local clinical samples and experiments. Comprehensive analysis showed that PKMYT1 expression was higher in BC tissues, especially in advanced patients than that in normal breast tissues. The expression of PKMYT1 was an independent determinant for BC patients’ prognosis when combined with the clinical features. In addition, based on multi-omics analysis, we found that the PKMYT1 expression was closely relevant to several oncogenic or tumor suppressor gene variants. The analysis of single-cell sequencing indicated that PKMYT1 expression was upregulated in triple-negative breast cancer (TNBC), consistent with the results of bulk RNA-sequencing. High PKMYT1 expression was correlated with a poor prognosis. Functional enrichment analysis revealed that PKMYT1 expression was associated with cell cycle-related, DNA replication-related, and cancer-related pathways. Further research revealed that PKMYT1 expression was linked to immune cell infiltration in the tumor microenvironment. Additionally, loss-of-function experiments in vitro were performed to investigate the role of PKMYT1. TNBC cell lines’ proliferation, migration, and invasion were inhibited when PKMYT1 expression was knock-down. Besides, the down-regulation of PKMYT1 induced apoptosis in vitro. As a result, PKMYT1 might be a biomarker for prognosis and a therapeutic target for TNBC. |
format | Online Article Text |
id | pubmed-9922894 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99228942023-02-14 Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer Li, Huihui Wang, Li Zhang, Wei Dong, Youting Cai, Yefeng Huang, Xiaoli Dong, Xubin Front Oncol Oncology Breast cancer (BC) is one of the most common malignancies among women worldwide. It is necessary to search for improvement in diagnosis and treatment methods to improve the prognosis. Protein kinase, membrane associated tyrosine/threonine 1 (PKMYT1), a member of the Wee family of protein kinases, has been studied in some tumors except BC. This study has explored that PKMYT1 functional role by bioinformatics methods combined with local clinical samples and experiments. Comprehensive analysis showed that PKMYT1 expression was higher in BC tissues, especially in advanced patients than that in normal breast tissues. The expression of PKMYT1 was an independent determinant for BC patients’ prognosis when combined with the clinical features. In addition, based on multi-omics analysis, we found that the PKMYT1 expression was closely relevant to several oncogenic or tumor suppressor gene variants. The analysis of single-cell sequencing indicated that PKMYT1 expression was upregulated in triple-negative breast cancer (TNBC), consistent with the results of bulk RNA-sequencing. High PKMYT1 expression was correlated with a poor prognosis. Functional enrichment analysis revealed that PKMYT1 expression was associated with cell cycle-related, DNA replication-related, and cancer-related pathways. Further research revealed that PKMYT1 expression was linked to immune cell infiltration in the tumor microenvironment. Additionally, loss-of-function experiments in vitro were performed to investigate the role of PKMYT1. TNBC cell lines’ proliferation, migration, and invasion were inhibited when PKMYT1 expression was knock-down. Besides, the down-regulation of PKMYT1 induced apoptosis in vitro. As a result, PKMYT1 might be a biomarker for prognosis and a therapeutic target for TNBC. Frontiers Media S.A. 2023-01-30 /pmc/articles/PMC9922894/ /pubmed/36793346 http://dx.doi.org/10.3389/fonc.2022.1002186 Text en Copyright © 2023 Li, Wang, Zhang, Dong, Cai, Huang and Dong https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Li, Huihui Wang, Li Zhang, Wei Dong, Youting Cai, Yefeng Huang, Xiaoli Dong, Xubin Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer |
title | Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer |
title_full | Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer |
title_fullStr | Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer |
title_full_unstemmed | Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer |
title_short | Overexpression of PKMYT1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer |
title_sort | overexpression of pkmyt1 associated with poor prognosis and immune infiltration may serve as a target in triple-negative breast cancer |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9922894/ https://www.ncbi.nlm.nih.gov/pubmed/36793346 http://dx.doi.org/10.3389/fonc.2022.1002186 |
work_keys_str_mv | AT lihuihui overexpressionofpkmyt1associatedwithpoorprognosisandimmuneinfiltrationmayserveasatargetintriplenegativebreastcancer AT wangli overexpressionofpkmyt1associatedwithpoorprognosisandimmuneinfiltrationmayserveasatargetintriplenegativebreastcancer AT zhangwei overexpressionofpkmyt1associatedwithpoorprognosisandimmuneinfiltrationmayserveasatargetintriplenegativebreastcancer AT dongyouting overexpressionofpkmyt1associatedwithpoorprognosisandimmuneinfiltrationmayserveasatargetintriplenegativebreastcancer AT caiyefeng overexpressionofpkmyt1associatedwithpoorprognosisandimmuneinfiltrationmayserveasatargetintriplenegativebreastcancer AT huangxiaoli overexpressionofpkmyt1associatedwithpoorprognosisandimmuneinfiltrationmayserveasatargetintriplenegativebreastcancer AT dongxubin overexpressionofpkmyt1associatedwithpoorprognosisandimmuneinfiltrationmayserveasatargetintriplenegativebreastcancer |