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Updated: May 11, 2026

Genome-wide Analysis using ChIP to Identify Isoform-specific Gene Targets
Published on: July 7, 2010
Histone demethylase RBP2 promotes lung tumorigenesis and cancer metastasis
Yu-Ching Teng1, Cheng-Feng Lee, Ying-Shiuan Li
1Genomics Research Center, Academia Sinica, 128, Academia Rd., Sec. 2, Nankang, Taipei, 115, Taiwan.
Abstract:
The retinoblastoma binding protein RBP2 (KDM5A) is a histone demethylase that promotes gastric cancer cell growth and is enriched in drug-resistant lung cancer cells. In tumor-prone mice lacking the tumor suppressor gene RB or MEN1, genetic ablation of RBP2 can suppress tumor initiation, but the pathogenic breadth and mechanistic aspects of this effect relative to human tumors have not been defined. Here, we approached this question in the context of lung cancer. RBP2 was overexpressed in human lung cancer tissues where its depletion impaired cell proliferation, motility, migration, invasion, and metastasis. RBP2 oncogenicity relied on its demethylase and DNA-binding activities. RBP2 upregulated expression of cyclins D1 and E1 while suppressing the expression of cyclin-dependent kinase inhibitor p27 (CDKN1B), each contributing to RBP2-mediated cell proliferation. Expression microarray analyses revealed that RBP2 promoted expression of integrin-β1 (ITGB1), which is implicated in lung cancer metastasis. Mechanistic investigations established that RBP2 bound directly to the p27, cyclin D1, and ITGB1 promoters and that exogenous expression of cyclin D1, cyclin E1, or ITGB1 was sufficient to rescue proliferation or migration/invasion, respectively. Taken together, our results establish an oncogenic role for RBP2 in lung tumorigenesis and progression and uncover novel RBP2 targets mediating this role.
Insights
Retinoblastoma binding protein RBP2 (KDM5A) drives lung cancer progression by promoting cell proliferation and metastasis. Its depletion suppresses tumor growth, revealing RBP2 as a potential therapeutic target for lung cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Retinoblastoma binding protein RBP2 (KDM5A) is a histone demethylase implicated in gastric cancer and drug-resistant lung cancer.
- Previous studies in mice suggest RBP2 ablation suppresses tumor initiation, but its role in human lung cancer requires further definition.
Purpose of the Study:
- To investigate the oncogenic role of RBP2 in human lung cancer.
- To elucidate the mechanisms by which RBP2 promotes lung tumorigenesis and progression.
Main Methods:
- Analysis of RBP2 expression in human lung cancer tissues.
- Assessment of RBP2 depletion effects on cancer cell proliferation, motility, invasion, and metastasis.
- Investigation of RBP2's demethylase and DNA-binding activities.
- Gene expression analysis (microarray) and promoter binding assays.
- Rescue experiments with target gene overexpression.
Main Results:
- RBP2 is overexpressed in human lung cancer, and its depletion inhibits proliferation, motility, invasion, and metastasis.
- RBP2 oncogenicity depends on its demethylase and DNA-binding activities.
- RBP2 upregulates cyclins D1/E1 and ITGB1 while downregulating p27 (CDKN1B), directly binding to their promoters.
- Overexpression of cyclin D1, cyclin E1, or ITGB1 rescues RBP2-mediated proliferation or invasion.
Conclusions:
- RBP2 plays a significant oncogenic role in lung cancer initiation and progression.
- RBP2 targets include cyclins D1/E1, p27, and ITGB1, mediating its effects on proliferation and metastasis.
- RBP2 represents a potential therapeutic target for lung cancer.
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