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...

Descripción completa

Detalles Bibliográficos
Autores principales: Li, Huihui, Wang, Li, Zhang, Wei, Dong, Youting, Cai, Yefeng, Huang, Xiaoli, Dong, Xubin
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