Knockdown Of TRIM31 Enhances Colorectal Cancer Radiosensitivity By Inducing DNA Damage And Activating Apoptosis

• Main Authors: Zhang H, Deng Y, Liang L, Shen L, Zhu J, Wang Y, Zhang J, Zhang Z
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-10-01
• Series: OncoTargets and Therapy
• Subjects: colorectal cancer; radiosensitivity; TRIM31
• Online Access: https://www.dovepress.com/knockdown-of-trim31-enhances-colorectal-cancer-radiosensitivity-by-ind-peer-reviewed-article-OTT
• ISSN: 1178-6930

Hui Zhang,1,2,* Yun Deng,1–3,* Liping Liang,1,2 Lijun Shen,1,2 Ji Zhu,1,2 Yaqi Wang,1,2 Jing Zhang,1,2 Zhen Zhang1,2 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 3Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhen ZhangDepartment of Radiotherapy, Fudan University Shanghai Cancer Center, 270 Dong An Road, Shanghai 200032, People’s Republic of ChinaTel [phone]-5210Fax [phone]Email [e-mail]: Biomarkers that predict radiosensitivity are essential for personalized radiotherapy. We performed microarray analysis for rectal cancer patients between those with good response and poor response to preoperative radiotherapy and found that patients with lower expression of tripartite motif-containing protein 31 (TRIM31) showed a better response. In this study, we confirmed the effects of TRIM31 on radiosensitivity by knockdown of TRIM31 in colorectal cancer cells.Methods and materials: Human colorectal cancer cell lines HT-29 and SW480, which are TRIM31 stably knocked-down, were used for analysis. We studied the level of DNA damage and the change of relative proteins after irradiation in TRIM31-knockdown cells. Flow cytometry was used to test for apoptosis, cell cycle stage, and reactive oxygen species (ROS) levels after irradiation. Cell survival was measured by cloning assay. Proteins related to DNA damage were evaluated by Western blotting.Results: The percentage of apoptotic cells and the levels of ROS were elevated, and the survival fraction was reduced in TRIM31-knockdown cells. The expression levels of the DNA damage proteins phosphorylated ataxia-telangiectasia mutation (P-ATM), DNA protein kinases (DNA-PKs), and γ-H2AX were higher in TRIM31-knockdown cells.Conclusion: Knockdown of TRIM31 increases DNA damage and radiosensitivity in colorectal cancer cells.Keywords: colorectal cancer, radiosensitivity, TRIM31