TRIM9 Interacts with ZEB1 to Suppress Esophageal Cancer by Promoting ZEB1 Protein Degradation via the UPP Pathway.

Zhaoxian Lin, Jianyuan Huang, Lihuan Zhu, Xing Lin, Yangyun Huang, Chun Chen, Xiaojie Pan

BioMed research international 2023

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Esophageal cancer remains one of the most lethal malignant diseases globally. Previous studies indicated that TRIM9 (Tripartite Motif Containing 9) is a potential marker in breast cancer patients. Therefore, in the current research, we intended to clarify the regulatory network of TRIM9 and its relative role in esophageal cancer patients. We aimed to elucidate the regulatory role of TRIM9 in esophageal cancer. Clinical tumor tissue samples combined with cancer cell line models were utilized to explore the TRIM9 expression pattern. Functional experiments including transwell assay, cell viability assay, and ubiquitination blocking experiments were performed to evaluate the role of the TRIM9/ZEB1 (zinc finger E-box binding homeobox 1) axis and UPP pathway in esophageal cancer progression and exacerbation. Both esophageal cancer samples and cell line models showed significantly suppressed levels of TRIM9. Functional experiments confirmed that TRIM9 overexpression inhibited the cell viability, invasiveness, and stem-like phenotype of cancer cells. Subsequent investigations suggested that TRIM9-ZEB1 interaction accelerated ZEB1 protein degradation through the modulation of the UPP pathway, which confirmed the protective role of TRIM9 in esophageal cancer progression and metastasis. This study concluded that TRIM9 was a tumor suppressor that interacted with ZEB1 and accelerated ZEB1 protein degradation via the ubiquitin-proteasome pathway (UPP). Our research emphasized TRIM9-ZEB1 interaction as a valuable target for esophageal cancer treatment in future development. More detailed studies are needed to further consolidate our findings. Copyright © 2023 Zhaoxian Lin et al.

Citation

Zhaoxian Lin, Jianyuan Huang, Lihuan Zhu, Xing Lin, Yangyun Huang, Chun Chen, Xiaojie Pan. TRIM9 Interacts with ZEB1 to Suppress Esophageal Cancer by Promoting ZEB1 Protein Degradation via the UPP Pathway. BioMed research international. 2023;2023:2942402