SPDYE3 promotes cell cycle and LUSC progression by regulating the CDC25C/CDK1 pathway

Zhuowei Shao; Jiankui Ye; Yili Wu; Yu Chen; Rong Wang; Shuai Fang; Shibo Wu

doi:10.1016/j.biocel.2025.106825

SPDYE3 promotes cell cycle and LUSC progression by regulating the CDC25C/CDK1 pathway

Int J Biochem Cell Biol. 2025 Jun 26:106825. doi: 10.1016/j.biocel.2025.106825. Online ahead of print.

Authors

Zhuowei Shao¹, Jiankui Ye¹, Yili Wu², Yu Chen², Rong Wang¹, Shuai Fang³, Shibo Wu⁴

Affiliations

¹ Department of Respiratory Medicine, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang, China.
² Department of Respiratory Medicine, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang, China; Health Science Center, Ningbo University, Ningbo, Zhejiang, China.
³ Department of Thoracic Surgery, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, Zhejiang, China.
⁴ Department of Respiratory Medicine, The Affiliated Lihuili Hospital of Ningbo University, Ningbo, Zhejiang, China. Electronic address: woshibo2015@yeah.net.

PMID: 40581088
DOI: 10.1016/j.biocel.2025.106825

Abstract

Background: Lung cancer is the primary reason for global cancer-related deaths. Targeted therapy is currently absent for lung squamous cell carcinoma (LUSC), a significant pathological subtype of lung cancer. The gene SPDYE3, a member of the Speedy/Ringo gene family, is highly expressed in different cancer tissues and functions as a cell cycle regulator. However, the potential mechanisms and clinical significance of SPDYE3 in LUSC remain unknown. METHOD：: Gene chip technology was used to detect the expression profiles of RNA in saliva, plasma, and normal controls of LUSC patients. Real-time quantitative polymerase chain reaction(qRT-PCR) was utilized to examine the expression and significance of SPDYE3 in the early diagnosis of LUSC. Furthermore, additional experiments were performed in vitro and in vivo to further assess the impact of SPDYE3 on the proliferation and cell cycle of LUSC. Further investigations were performed using IP, mass spectrometry analysis, and Western blotting to explore the interaction between SPDYE3 and cell division cycle 25C (CDC25C).

Result: Our data showed that SPDYE3 is upregulated in LUSC tissues, plasma, and cells. SPDYE3 exhibited diagnostic usefulness, achieving an Area Under the Curve (AUC) of 0.7288. Experiments conducted in vitro and in vivo revealed that SPDYE3 enhances the growth and advancement of the cell cycle in LUSC cells. SPDYE3 mechanistically stimulates the activation of cyclin-dependent kinase 1 (CDK1) and controls the advancement of the cell cycle by interacting with CDC25C.

Conclusion: Overall, our results support the novel regulatory role of SPDYE3 in LUSC cell cycle progression mechanisms by influencing the CDC25C/CDK1 signaling pathway.

Keywords: CDC25C; CDK1; SPDYE3; cell cycle; lung squamous cell carcinoma.