RRM2 regulates the high expression of PD-L1 via the ERK signaling pathway to play a cancer-promoting role in cervical cancer

Xieyidai Abuduhailili; Yangchun Feng; Ruijiao Lu; Yuxia Li; Senyu Wang

doi:10.1016/j.prp.2025.156114

RRM2 regulates the high expression of PD-L1 via the ERK signaling pathway to play a cancer-promoting role in cervical cancer

Pathol Res Pract. 2025 Jul 9:272:156114. doi: 10.1016/j.prp.2025.156114. Online ahead of print.

Authors

Xieyidai Abuduhailili¹, Yangchun Feng², Ruijiao Lu³, Yuxia Li³, Senyu Wang⁴

Affiliations

¹ Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi 830011, China. Electronic address: 2508815542@qq.com.
² Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi 830011, China. Electronic address: paopao1987123@163.com.
³ Clinical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, Urumqi 830011, China.
⁴ Department of Clinical Laboratory, the Second Affiliated Hospital of Xinjiang Medical University, Urumqi 830011, China. Electronic address: 18040823473@163.com.

PMID: 40651124
DOI: 10.1016/j.prp.2025.156114

Abstract

Background: Cervical cancer is one of the most common malignant tumors in women. Ribonucleotide reductase M2 (RRM2) plays a key role in tumor occurrence and progression. This study aimed to investigate the role of RRM2 in cervical cancer and its potential mechanism.

Methods: Ribonucleotide reductase M2 expression and its association with immune cell infiltration were assessed using bioinformatics analysis. Functional enrichment analysis of RRM2 and its coexpressed genes was performed. Furthermore, correlations between RRM2 and ERK1/2 and PD-L1 expressions were analyzed. In vitro and in vivo experiments, including quantitative real-time PCR, western blotting, flow cytometry, the Cell Counting Kit-8 assay, the TUNEL assay, and hematoxylin-eosin staining, were conducted to analyze the effects of RRM2 on ERK1/2 and PD-L1 expression and the malignant phenotype of cervical cells.

Results: Ribonucleotide reductase M2 was highly expressed in cervical cancer tissues compared with adjacent normal tissues and was negatively associated with immune cell infiltration and overall survival. Its knockdown suppressed proliferation, migration, and invasion and increased apoptosis. Mechanistically, RRM2 may promote cervical cancer development by upregulating ERK1/2 and PD-L1 progression in vitro and in vivo.

Conclusion: Ribonucleotide reductase M2 promotes cervical cancer progression and positively regulates PD-L1 expression through the ERK signaling pathway.

Keywords: Cervical cancer; ERK signaling pathway; PD-L1; RRM2.