KDM6B Elicits Cell Apoptosis by Promoting Nuclear Translocation of FOXO1 in Non-Small Cell Lung Cancer.

Abstract

BACKGROUND/AIMS:

Non-small cell lung carcinoma (NSCLC) is the most common type of lung cancer and the cause of most cancer-related deaths. The molecular mechanisms that are involved in NSCLC development are currently not well understood. Accumulating evidence shows that histone demethylases play important roles in the regulation of pathological developmental processes in many diseases, including various types of cancers.

METHODS:

Mitochondrial membrane potential assays, migration and invasion assays, caspase-3 and caspase-9 activity assays and western blot analysis were used in this research.

RESULTS:

We found that overexpression of KDM6B, a demethylase that acts on histone H3 at lysine 27 (H3K27), inhibited cell growth by initiating mitochondria-dependent apoptosis and by attenuating the invasion-metastasis cascade in NSCLC cells. Moreover, our results showed that KDM6B directly interacted with FOXO1 and that overexpression of KDM6B promoted nuclear accumulation of FOXO1. The effects of KDM6B on cell apoptosis and metastasis were weakened by knockdown of FOXO1 expression. On the contrary, knocking down expression of KDM6B inhibited cell apoptosis and promoted cell growth by mitigating the nuclear translocation of FOXO1 in NSCLC cells.

CONCLUSIONS:

These findings suggest that KDM6B may act in a pro-apoptotic role in NSCLC by causing the nuclear translocation of FOXO1.

• Authors: Jun Ma, Ning Wang, Yurong Zhang, Cun Wang, Tianxiang Ge, Haojie Jin, Xuan Deng, Xisong Huo, Dishui Gu, Zhouhong Ge, Wei Chu, Liyan Jiang, Wenxin Qin
• Journal: Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology (Cell Physiol Biochem) Vol. 37 Issue 1 Pg. 201-13 ( 2015) ISSN: 1421-9778 [Electronic] Germany
• PMID: 26303949 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 S. Karger AG, Basel.

Chemical References

• FOXO1 protein, human
• Forkhead Box Protein O1
• Forkhead Transcription Factors
• Histones
• Histone Demethylases
• Jumonji Domain-Containing Histone Demethylases
• KDM6B protein, human
• Caspase 3
• Caspase 9

Topics

• Apoptosis (genetics, physiology)
• Carcinoma, Non-Small-Cell Lung (genetics, metabolism, pathology)
• Caspase 3 (metabolism)
• Caspase 9 (metabolism)
• Cell Line, Tumor
• Cell Movement (genetics, physiology)
• Cell Proliferation (genetics, physiology)
• Forkhead Box Protein O1
• Forkhead Transcription Factors (metabolism)
• Gene Expression Regulation, Neoplastic (genetics, physiology)
• Histone Demethylases (metabolism)
• Histones (metabolism)
• Humans
• Jumonji Domain-Containing Histone Demethylases (metabolism)
• Lung Neoplasms (genetics, metabolism, pathology)
• Membrane Potential, Mitochondrial (genetics, physiology)
• Mitochondria (genetics, metabolism)
• Protein Transport (genetics)