HBP1 promoter methylation augments the oncogenic β-catenin to correlate with prognosis in NSCLC

Ruo Chia Tseng, Way Ren Huang, Su Feng Lin, Pei Chen Wu, Han Shui Hsu, Yi-Ching Wang

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1752-1761
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Volume18
Issue number9
DOIs
Publication statusPublished - 2014 Sep 1

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Catenins
Non-Small Cell Lung Carcinoma
Methylation
Transcriptional Activation
Neoplasms
Gene Deletion
Colonic Neoplasms
Lung Neoplasms
Proteins
Transcription Factors
Biomarkers
Immunohistochemistry
Breast Neoplasms
Messenger RNA
Mutation
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Cell Biology

Cite this

Tseng, Ruo Chia ; Huang, Way Ren ; Lin, Su Feng ; Wu, Pei Chen ; Hsu, Han Shui ; Wang, Yi-Ching. / HBP1 promoter methylation augments the oncogenic β-catenin to correlate with prognosis in NSCLC. In: Journal of Cellular and Molecular Medicine. 2014 ; Vol. 18, No. 9. pp. 1752-1761.
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abstract = "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.",
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HBP1 promoter methylation augments the oncogenic β-catenin to correlate with prognosis in NSCLC. / Tseng, Ruo Chia; Huang, Way Ren; Lin, Su Feng; Wu, Pei Chen; Hsu, Han Shui; Wang, Yi-Ching.

In: Journal of Cellular and Molecular Medicine, Vol. 18, No. 9, 01.09.2014, p. 1752-1761.

Research output: Contribution to journalArticle

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T1 - HBP1 promoter methylation augments the oncogenic β-catenin to correlate with prognosis in NSCLC

AU - Tseng, Ruo Chia

AU - Huang, Way Ren

AU - Lin, Su Feng

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