2. Academic Validation
  3. PSME2 promotes malignant progression through autophagy modulation via IL-6/STAT3 signaling pathway in esophageal squamous cell carcinoma

PSME2 promotes malignant progression through autophagy modulation via IL-6/STAT3 signaling pathway in esophageal squamous cell carcinoma

  • Life Sci. 2025 Sep 1:376:123749. doi: 10.1016/j.lfs.2025.123749.
Kui Sun 1,  Yong-Xuan Liu 1,  Meng-Xiang Li 2,  Chun-Hui Qi 1,  Xiao-Shuang Wu 1,  Yong-An Kang 1,  Di Zhao 1,  Zi-Chao Zhang 1,  Yu-Bo Du 1,  She-Gan Gao 3,  Yi-Jun Qi 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Esophageal Cancer Prevention & Treatment, Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang 471003, China.
  • 2 Department of Mathematics and Physics, Luoyang Institute of Science and Technology, Luoyang 471023, China.
  • 3 State Key Laboratory of Esophageal Cancer Prevention & Treatment, Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang 471003, China. Electronic address: gsg112258@haust.edu.cn.
  • 4 State Key Laboratory of Esophageal Cancer Prevention & Treatment, Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment, Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang 471003, China. Electronic address: qiyijun@haust.edu.cn.
PMID: 40404117 DOI: 10.1016/j.lfs.2025.123749
Abstract

Aims: This study aims to investigate the expression, clinical relevance, and functional roles of PSME2 in esophageal squamous cell carcinoma (ESCC).

Materials and methods: The biomarkers for ESCC were identified through comprehensive analysis of publicly available mRNA transcriptome data obtained from TCGA and GEO databases. The mRNA and protein expression levels of PSME2 in ESCC were validated using two independent cohorts of ESCC samples. The proliferation, migration, invasion, and Autophagy activity of ESCC cells were evaluated in vitro through the knockdown of PSME2 or PR171. The effects of the knockdown of PSME2, STAT3 Inhibitor WP1066, and Autophagy inhibitor chloroquine on the tumorigenic potential of ESCC cells were also assessed through an in vivo subcutaneous tumor model established in nude mice.

Key findings: The result obtained indicates the upregulation of PSME2 in ESCC, suggesting poor prognosis. The result also shows that the knockdown of PSME2 and PR171 triggers the reduction in ESCC cell proliferation, migration, and invasion. Thus, it buttresses the fact that PSME2 knockdown induced Autophagy through the IL6/STAT3 pathway, leading to cell death resistance. The result also linked the suppression of tumor growth to the knockdown of PSME2 and WP1066 or chloroquine, suggesting that targeting these proteins may be a potential therapeutic strategy for inhibiting tumor progression.

Significance: The study shows the promising role of PSME2 as a therapeutic target in ESCC management. The combined inhibition of PSME2 and activated pathways ensures effective suppression of tumor growth and proliferation, thus offering a novel strategy for better treatment outcomes in ESCC patients.

Keywords

Autophagy modulation; Cancer cell survival; IL-6/STAT3 pathway; Proteasome; Tumor progression.

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