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ONECUT2 overexpression promotes RAS-driven lung adenocarcinoma progression
Qingyang Ma1, Kai Wu1,2, Hui Li1,2
1CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
Scientific Reports
|December 29, 2019
Summary
Aberrant gene activation drives cancer. Researchers found the gene ONECUT2 promotes lung cancer growth and metastasis by altering cell identity, suggesting it as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- Aberrant differentiation, involving activation of silent tissue-specific genes, can lead to cell identity changes and cancer progression.
- The genetic and epigenetic mechanisms driving these changes remain largely unknown.
Purpose of the Study:
- To investigate the role of ectopic gene activation in lung cancer development.
- To identify specific genes and pathways involved in lung cancer progression and metastasis.
Main Methods:
- Analysis of ONECUT2 gene expression across lung cancer subtypes.
- In vitro and in vivo studies using A549 lung cancer cells to assess the functional impact of ONECUT2.
- Integrative transcriptomic and epigenomic analyses to elucidate the molecular mechanisms of ONECUT2 action.
Main Results:
- Ectopic activation of the gene one cut homeobox 2 (ONECUT2) was observed in various lung cancer subtypes.
- ONECUT2 expression correlated with poor prognosis in RAS-driven lung adenocarcinoma.
- ONECUT2 overexpression enhanced lung cancer cell proliferation, invasion, tumorigenesis, and bone metastasis.
- ONECUT2 was found to promote cell trans-differentiation by regulating bivalent chromatin domains via Polycomb Repressive Complex 2 (PRC2) modulation.
Conclusions:
- ONECUT2 acts as a lineage-specific and context-dependent oncogene in lung adenocarcinoma.
- Targeting ONECUT2 may offer a novel therapeutic strategy for lung adenocarcinoma patients.
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