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SHOX2 regulates TRIM29 to enhance malignant progression and EMT in lung squamous cell carcinoma
Zhiliang Huang1, Manli Yan2, Junru Liu2
1Department of Cardiovascular Thoracic Surgery, The Fifth Hospital of Wuhan, Wuhan 430050, Hubei, China; Department of Cardiovascular Thoracic Surgery, The Sixth Hospital of Wuhan, Wuhan 430015, Hubei, China.
Background:
Lung squamous cell carcinoma (LUSC) is a prevalent subtype pulmonary malignancy, characterized by high incidence and mortality rates. Previous research has highlighted the aberrant TRIM29 expression in various tumor tissues, yet investigations into its specific function remain limited.
Methods:
The GEPIA database and Kaplan-Meier Plotter database were used to assess TRIM29 expression in LUSC. TRIM29 expression in paired LUSC tumor and adjacent normal tissues as well as in LUSC cell lines was detected by immunohistochemistry, western blot, and qRT-PCR. CCK-8, EdU and colony formation assay were carried out to evaluate cell proliferation. Migration and invasion ability were measured by transwell assay. The expression levels of EMT-related proteins in LUSC cells were detected by western blot. The HumanTFDB was used to predict transcription factors that interact with TRIM29. Luciferase assay and ChIP assay were used to verify their targeting binding between them. Rescue experiments confirmed the binding interaction between TRIM29 and SHOX2.
Results:
This study unveiled substantial upregulation of both TRIM29 and SHOX2 in LUSC tissues and cells. Functional in vitro experiments validated that knockdown of TRIM29 notably impeded the malignant phenotype of LUSC, suppressed epithelial-mesenchymal transition (EMT) progression and induced cell apoptosis. Bioinformatics analysis and rescue experiments uncovered that the transcription factor SHOX2 positively regulates TRIM29, influencing LUSC occurrence and progression.
Conclusions:
These research findings suggest that the regulatory influence of SHOX2 on TRIM29 enhanced the malignant progression and the EMT process in LUSC, presenting potential new avenues for both its diagnosis and treatment.