HBP1 promoter methylation augments the oncogenic β-catenin to correlate with prognosis in NSCLC
| Autor: | Ruo Chia Tseng, Way Ren Huang, Su Feng Lin, Pei Chen Wu, Han Shui Hsu, Yi Ching Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Transcriptional Activation
Lung Neoplasms Repressor Gene Expression Kaplan-Meier Estimate Biology NSCLC transcriptional repressor Transactivation Carcinoma Non-Small-Cell Lung Cell Line Tumor Gene expression medicine HBP1 Humans Prospective Studies RNA Messenger Lung cancer Promoter Regions Genetic beta Catenin Proportional Hazards Models Gene knockdown Tumor Suppressor Proteins High Mobility Group Proteins Cancer Cell Biology Original Articles β-catenin DNA Methylation medicine.disease Prognosis Gene Expression Regulation Neoplastic Repressor Proteins DNA methylation Cancer research Molecular Medicine Ectopic expression |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| Popis: | β-catenin nuclear accumulation is frequently identified in human non-small cell lung cancer (NSCLC). The HMG-box transcription factor 1 (HBP1) is a known repressor of β-catenin transactivation. However, the role of HBP1 in relation to β-catenin nuclear accumulation has not been addressed in human cancer patients. In addition, the mechanism of HBP1 gene alteration in NSCLC remains unclear, although HBP1 mutation and gene deletion of HBP1 are reported in breast and colon cancers. Here, we demonstrate that HBP1 acts as a tumour suppressor and serves as a prognostic biomarker in NSCLC clinical and cell models. The immunohistochemistry data indicated that 30.5% (25/82) of tumours from NSCLC patients showed absence or low expression of HBP1 protein. A significant inverse correlation between mRNA/protein expression and promoter hypermethylation suggested that promoter hypermethylation is responsible for low expression of HBP1 in NSCLC patients. Reactivation of HBP1 expression by demethylation reagent or ectopic expression of HBP1 suppressed β-catenin transactivation. Conversely, HBP1 knockdown increased β-catenin transactivation. Importantly, preserved expression of HBP1 had a significantly protective effect on prognosis in patients with β-catenin nuclear accumulation, suggesting that low expression of HBP1 in NSCLC patients with β-catenin nuclear accumulation was one of the major determinants of prognosis. Our data from cellular and clinical models suggest that HBP1 is a suppressor of cancer progression, making it a potential prognostic predictor and therapeutic target to attenuate lung cancer progression. |
| Databáze: | OpenAIRE |
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