Research Papers:

Methylation of promoter of RBL1 enhances the radioresistance of three dimensional cultured carcinoma cells

Dong Pan, Yaxiong Chen, Yarong Du, Zhenxin Ren, Xiaoman Li and Burong Hu _

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Oncotarget. 2017; 8:4422-4435. https://doi.org/10.18632/oncotarget.12647

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Dong Pan1,2, Yaxiong Chen1, Yarong Du1, Zhenxin Ren1, Xiaoman Li1,2, Burong Hu1,3

1Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences & Key Laboratory of Space Radiobiology of Gansu Province, Institute of Modern Physics, Chinese Academy of Sciences, Lanzhou, China

2University of Chinese Academy of Sciences, Beijing, China

3Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou, Jiangsu, China

Correspondence to:

Burong Hu, email: [email protected]

Keywords: three dimensional cultured cells, radioresistance, methylation, promoter, RBL1

Received: August 04, 2016    Accepted: September 29, 2016    Published: October 13, 2016


Three dimensional (3D) culture in vitro is a new cell culture model that more closely mimics the physiology features of the in vivo environment and is being used widely in the field of medical and biological research. It has been demonstrated that cancer cells cultured in 3D matrices are more radioresistant compared with cells in monolayer (2D). However, the mechanisms causing this difference remain largely unclear. Here we found that the cell cycle distribution and expression of cell cycle regulation genes in 3D A549 cells are different from the 2D. The higher levels of the promotor methylation of cell cycle regulation genes such as RBL1 were observed in 3D A549 cells compared with cells in 2D. The treatments of irradiation or 5-Aza-CdR activated the demethylation of RBL1 promotor and resulted in the increased expression of RBL1 only in 3D A549 cells. Inhibition of RBL1 enhanced the radioresistance and decreased the G2/M phase arrest induced by irradiation in 2D A549 and MCF7 cells. Overexpression of RBL1 sensitized 3D cultured A549 and MCF7 cells to irradiation. Taken together, to our knowledge, it is the first time to revealthat the low expression of RBL1 due to itself promotor methylation in 3D cells enhances the radioresistance. Our finding sheds a new light on understanding the features of the 3D cultured cell model and its application in basic research into cancer radiotherapy and medcine development.

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