Kinome-Wide siRNA Screening Identifies DYRK1B as a Potential Therapeutic Target for Triple-Negative Breast Cancer Cells

Aims: The selective molecules for targeted therapy of triple-negative breast cancer (TNBC) are limited. Several kinases play pivotal roles in cancer development and malignancy. The study aims to determine if any kinases confer to malignancy of TNBC cells, which could serve as a theranostic target fo...

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Autores principales:	Chia-Che Chang, Chien-Chih Chiu, Pei-Feng Liu, Chih-Hsuan Wu, Yen-Chiang Tseng, Cheng-Hsin Lee, Chih-Wen Shu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	kinome siRNA screening DYRK1B prognosis triple-negative breast cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/2540cff0fcd14bddb898526a1af215ef
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spelling	oai:doaj.org-article:2540cff0fcd14bddb898526a1af215ef2021-11-25T17:03:54ZKinome-Wide siRNA Screening Identifies DYRK1B as a Potential Therapeutic Target for Triple-Negative Breast Cancer Cells10.3390/cancers132257792072-6694https://doaj.org/article/2540cff0fcd14bddb898526a1af215ef2021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5779https://doaj.org/toc/2072-6694Aims: The selective molecules for targeted therapy of triple-negative breast cancer (TNBC) are limited. Several kinases play pivotal roles in cancer development and malignancy. The study aims to determine if any kinases confer to malignancy of TNBC cells, which could serve as a theranostic target for TNBC. Methods: Kinome siRNA library was used to screen selective genes required for the proliferation of TNBC cells. The involvement of DYRK1B in cancer malignancy was evaluated with migration, invasion assays, and spheroid culture. The expression of DYRK1B was confirmed with quantitative PCR and immunoblotting. The clinical correlation of DYRK1B in TNBC patients was examined with tissue microarray and The Cancer Genome Atlas (TCGA) database. Results: Our results showed that silencing DYRK1B significantly suppressed cell viability in DYRK1B-high expressed TNBC cells, likely by arresting the cell cycle at the G<sub>1</sub> phase. Nevertheless, silencing DYRK1B had marginal effects on DYRK1B-low expressed TNBC cells. Similarly, the knockdown of DYRK1B decreased tumorsphere formation and increased cell death of the tumorsphere. Moreover, inactivation of DYRK1B by either specific inhibitor or ectopic expressing catalytic mutant of DYRK1B inhibited cell viability and metastatic characteristics, including migration and invasion. In addition, DYRK1B protein expression was elevated in tumor tissues compared to that in adjacent normal tissues of TNBC patients. Further, DYRK1B gene expression was highly correlated with CCDC97 or ZNF581 genes in TNBC cells and patients. High co-expression of DYRK1B with CCDC97 or ZNF581 was significantly associated with unfavorable overall survival and disease-free survival of TNBC patients. Conclusions: our results suggest DYRK1B might be essential for promoting tumor progression and could be a theranostic target for TNBC. Silencing or inactivation of DYRK1B might be a potential targeted therapy for TNBC.Chia-Che ChangChien-Chih ChiuPei-Feng LiuChih-Hsuan WuYen-Chiang TsengCheng-Hsin LeeChih-Wen ShuMDPI AGarticlekinomesiRNAscreeningDYRK1Bprognosistriple-negative breast cancerNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5779, p 5779 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	kinome siRNA screening DYRK1B prognosis triple-negative breast cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	kinome siRNA screening DYRK1B prognosis triple-negative breast cancer Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Chia-Che Chang Chien-Chih Chiu Pei-Feng Liu Chih-Hsuan Wu Yen-Chiang Tseng Cheng-Hsin Lee Chih-Wen Shu Kinome-Wide siRNA Screening Identifies DYRK1B as a Potential Therapeutic Target for Triple-Negative Breast Cancer Cells
description	Aims: The selective molecules for targeted therapy of triple-negative breast cancer (TNBC) are limited. Several kinases play pivotal roles in cancer development and malignancy. The study aims to determine if any kinases confer to malignancy of TNBC cells, which could serve as a theranostic target for TNBC. Methods: Kinome siRNA library was used to screen selective genes required for the proliferation of TNBC cells. The involvement of DYRK1B in cancer malignancy was evaluated with migration, invasion assays, and spheroid culture. The expression of DYRK1B was confirmed with quantitative PCR and immunoblotting. The clinical correlation of DYRK1B in TNBC patients was examined with tissue microarray and The Cancer Genome Atlas (TCGA) database. Results: Our results showed that silencing DYRK1B significantly suppressed cell viability in DYRK1B-high expressed TNBC cells, likely by arresting the cell cycle at the G<sub>1</sub> phase. Nevertheless, silencing DYRK1B had marginal effects on DYRK1B-low expressed TNBC cells. Similarly, the knockdown of DYRK1B decreased tumorsphere formation and increased cell death of the tumorsphere. Moreover, inactivation of DYRK1B by either specific inhibitor or ectopic expressing catalytic mutant of DYRK1B inhibited cell viability and metastatic characteristics, including migration and invasion. In addition, DYRK1B protein expression was elevated in tumor tissues compared to that in adjacent normal tissues of TNBC patients. Further, DYRK1B gene expression was highly correlated with CCDC97 or ZNF581 genes in TNBC cells and patients. High co-expression of DYRK1B with CCDC97 or ZNF581 was significantly associated with unfavorable overall survival and disease-free survival of TNBC patients. Conclusions: our results suggest DYRK1B might be essential for promoting tumor progression and could be a theranostic target for TNBC. Silencing or inactivation of DYRK1B might be a potential targeted therapy for TNBC.
format	article
author	Chia-Che Chang Chien-Chih Chiu Pei-Feng Liu Chih-Hsuan Wu Yen-Chiang Tseng Cheng-Hsin Lee Chih-Wen Shu
author_facet	Chia-Che Chang Chien-Chih Chiu Pei-Feng Liu Chih-Hsuan Wu Yen-Chiang Tseng Cheng-Hsin Lee Chih-Wen Shu
author_sort	Chia-Che Chang
title	Kinome-Wide siRNA Screening Identifies DYRK1B as a Potential Therapeutic Target for Triple-Negative Breast Cancer Cells
title_short	Kinome-Wide siRNA Screening Identifies DYRK1B as a Potential Therapeutic Target for Triple-Negative Breast Cancer Cells
title_full	Kinome-Wide siRNA Screening Identifies DYRK1B as a Potential Therapeutic Target for Triple-Negative Breast Cancer Cells
title_fullStr	Kinome-Wide siRNA Screening Identifies DYRK1B as a Potential Therapeutic Target for Triple-Negative Breast Cancer Cells
title_full_unstemmed	Kinome-Wide siRNA Screening Identifies DYRK1B as a Potential Therapeutic Target for Triple-Negative Breast Cancer Cells
title_sort	kinome-wide sirna screening identifies dyrk1b as a potential therapeutic target for triple-negative breast cancer cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/2540cff0fcd14bddb898526a1af215ef
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Kinome-Wide siRNA Screening Identifies DYRK1B as a Potential Therapeutic Target for Triple-Negative Breast Cancer Cells

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