Dual-specificity tyrosine-regulated kinase 2 exerts anti-tumor effects by induction of G1 arrest in lung adenocarcinoma

Lung cancer is a leading cause of cancer-related mortality and remains one of the most poorly prognosed disease worldwide. Therefore, it is necessary to identify novel molecular markers with potential therapeutic effects. Recent findings have suggested that dual-specificity tyrosine-regulated kinase...

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Vydané v:	Biochimica et biophysica acta. General subjects Ročník 1868; číslo 6; s. 130600
Hlavní autori:	Harada, Eriko, Yoshida, Saishu, Imaizumi, Yuta, Kawamura, Akira, Ohtsuka, Takashi, Yoshida, Kiyotsugu
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Netherlands Elsevier B.V 01.06.2024
Predmet:	A549 Cells adenocarcinoma Adenocarcinoma of Lung - genetics Adenocarcinoma of Lung - metabolism Adenocarcinoma of Lung - pathology Animals biomarkers breasts cell cycle Cell Line, Tumor Cell Proliferation Dyrk Kinases DYRK2 epithelium flow cytometry G1 arrest G1 Phase Cell Cycle Checkpoints - genetics Gene Expression Regulation, Neoplastic Humans immunoblotting Lung adenocarcinoma lung neoplasms Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - pathology lungs Mice Mice, SCID mortality neoplasm cells p21 p53 Protein Serine-Threonine Kinases - genetics Protein Serine-Threonine Kinases - metabolism Protein-Tyrosine Kinases - genetics Protein-Tyrosine Kinases - metabolism Xenograft Model Antitumor Assays xenotransplantation DYRK2 Lung adenocarcinoma G1 arrest p21 p53
ISSN:	0304-4165, 1872-8006, 1872-8006
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Popis
Shrnutí:	Lung cancer is a leading cause of cancer-related mortality and remains one of the most poorly prognosed disease worldwide. Therefore, it is necessary to identify novel molecular markers with potential therapeutic effects. Recent findings have suggested that dual-specificity tyrosine-regulated kinase 2 (DYRK2) plays a tumor suppressive role in colorectal, breast, and hepatic cancers; however, its effect and mechanism in lung cancer remain poorly understood. Therefore, this study aimed to investigate the tumor-suppressive role and molecular mechanism of DYRK2 in lung adenocarcinoma (LUAD) by in vitro experiments and xenograft models. The evaluation of DYRK2 expression was carried out using lung cancer cell lines and normal bronchial epithelial cells. Overexpression of DYRK2 was induced by an adenovirus vector, and cell proliferation was assessed through MTS assay and Colony Formation Assay. Cell cycle analysis was performed using flow cytometry. Additionally, proliferative capacity was evaluated in a xenograft model by subcutaneously implanting A549 cells into SCID mice (C·B17/Icr-scidjcl-scid/scid). Immunoblotting assays showed that DYRK2 was downregulated in most LUAD cell lines. DYRK2 overexpression using adenovirus vectors significantly suppressed cell proliferation compared with that in the control group. Additionally, DYRK2 overexpression suppressed tumor growth in a murine subcutaneous xenograft model. Mechanistically, DYRK2 overexpression inhibited the proliferation of LUAD cells via p21-mediated G1 arrest, which was contingent on p53. Taken together, these findings suggest that DYRK2 may serve as potential prognostic biomarker and therapeutic target for LUAD. •DYRK2 overexpression suppresses lung adenocarcinoma via p53 and p21 upregulation.•DYRK2 induces G1 arrest in lung adenocarcinoma cell lines.•DYRK2 expression may be a prognostic factor in lung adenocarcinoma.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0304-4165 1872-8006 1872-8006
DOI:	10.1016/j.bbagen.2024.130600