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

Autor: Harada E; Department of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan; Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan., Yoshida S; Department of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan., Imaizumi Y; Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan., Kawamura A; Department of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan., Ohtsuka T; Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan., Yoshida K; Department of Biochemistry, The Jikei University School of Medicine, Tokyo, Japan. Electronic address: kyoshida@jikei.ac.jp.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. General subjects [Biochim Biophys Acta Gen Subj] 2024 Jun; Vol. 1868 (6), pp. 130600. Date of Electronic Publication: 2024 Mar 18.
DOI: 10.1016/j.bbagen.2024.130600
Abstrakt: Objectives: 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.
Materials and Methods: 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).
Results: 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.
Conclusion: Taken together, these findings suggest that DYRK2 may serve as potential prognostic biomarker and therapeutic target for LUAD.
Competing Interests: Declaration of competing interest The authors declare no conflicts of interest associated with this manuscript.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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