Role of alphaII-spectrin and XPF interaction in Hepatocellular carcinoma

Chen Chi; Jian-Ang Chen; Ri-Xu Lin; Pei-Zhen Wang; Meng-Jun Hu; Guo-Rong Chen; Han-Bin Chen

doi:10.1016/j.gene.2025.149602

Role of alphaII-spectrin and XPF interaction in Hepatocellular carcinoma

Gene. 2025 Jun 2:963:149602. doi: 10.1016/j.gene.2025.149602. Online ahead of print.

Authors

Chen Chi¹, Jian-Ang Chen², Ri-Xu Lin³, Pei-Zhen Wang⁴, Meng-Jun Hu⁵, Guo-Rong Chen⁶, Han-Bin Chen⁷

Affiliations

¹ Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000 Zhejiang Province, China. Electronic address: 15825650619@163.com.
² Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000 Zhejiang Province, China. Electronic address: CJianAng@163.com.
³ Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000 Zhejiang Province, China. Electronic address: linrixu316@163.com.
⁴ Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000 Zhejiang Province, China. Electronic address: wpz123@wmu.edu.cn.
⁵ Department of Pathology, Zhuji People's Hospital, Shaoxing 312000 Zhejiang Province, China. Electronic address: hu-menjun@163.com.
⁶ Department of Pathology, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000 Zhejiang Province, China. Electronic address: chengr1978@sina.com.
⁷ Department of Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000 Zhejiang Province, China. Electronic address: chenhanbin@wmu.edu.cn.

PMID: 40466963
DOI: 10.1016/j.gene.2025.149602

Abstract

Background: Hepatocellular carcinoma (HCC) is a highly malignant digestive tumor with a poor prognosis. AlphaII-spectrin shows altered levels in various tumor tissues, indicating its significant role in tumor development. Xeroderma pigmentosum group F (XPF) is a nucleotide excision repair (NER)-related DNA repair endonuclease. Literature demonstrated that alphaII-spectrin recruits XPF for DNA repair, influencing tumor development. However, the relationship between these two proteins and HCC has not been reported.

Materials and methods: Bioinformatics was used to analyze the relationship between alphaII-spectrin expression and patient prognosis in HCC. Further Western blot, Immunohistochemistry and RT-qPCR were used to verify alphaII-spectrin expression in HCC. The relationship between alphaII-spectrin knockdown and proliferation, migration and invasion of HCC cell lines was verified by cell experiments. Additionally, proteomics experiments were designed to explore the roles and mechanisms of alphaII-spectrin and XPF. Finally, we further verified the relationship between XPF and HCC through in vitro experiments.

Results: The expression level of alphaII-spectrin in HCC tissues was significantly higher than that in paracancer tissues. Kaplan-Meier survival analysis showed that high alphaII-spectrin expression was associated with poor overall survival (OS) and short Disease-free survival (DFS) in HCC patients. Knockdown of alphaII-spectrin reduced the motility, invasion, and proliferation abilities of HCC cells. The expression level of XPF in HCC tissues was significantly higher than that in paracancer tissues. Knockdown of XPF reduced the proliferation abilities of HCC cells. Furthermore, we identified an interaction between alphaII-spectrin and XPF in HCC cells, with alphaII-spectrin affecting the proliferative ability of HCC cells by altering the functional state of XPF.

Conclusion: In summary, downregulation of alphaII-spectrin expression can inhibit the physiological processes of HCC, and this effect is related to XPF.

Keywords: AlphaII-spectrin; Hepatocellular carcinoma; Oncogene; Prognosis; XPF.