miR-4443 promotes radiation resistance of esophageal squamous cell carcinoma via targeting PTPRJ

Journal of Translational Medicine

Research

Xiaoxiao Liu¹  Yu Hao¹  Hongbing Ma¹  Shupei Pan¹  Wei Guo¹  Yuchen Wang¹  Xiaobo Shi¹  Shan Huang¹  Yue Ke¹ 

[1] Department of Radiation Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, No. 157, Xi Wu Road, 710004, Xi’an, China;

关键词: Esophageal squamous cell carcinoma;    Radioresistance;    WGCNA;    miR-4443/PTPRJ axis;    Apoptosis;   

DOI  :  10.1186/s12967-022-03818-5

 received in 2022-10-31, accepted in 2022-12-08,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundRadiotherapy is one of the main treatments for esophageal squamous cell carcinoma (ESCC), but its efficacy is limited by radioresistance. MicroRNAs play a crucial role in posttranscriptional regulation, which is linked to the cancer response to radiation.MethodsWe successfully established a radioresistant cell line model by using fractionated irradiation. qRT-PCR was adopted to detect the expression of miR-4443 in human normal esophageal cell lines, tumor cells, and radioresistant cells. Next, CCK-8, colony formation, apoptosis, and cell cycle assays were used to assess the biological effect of miR-4443. Weighted gene coexpression network analysis (WGCNA) was performed to identify potential radiosensitivity-related genes. Additionally, we predicted the probable targets of the miRNA using bioinformatic methods and confirmed them using Western blot.ResultsmiR-4443 was significantly upregulated in radioresistant ESCC cells. Enhancement of miR-4443 further decreased the radiosensitivity of ESCC cells, while inhibition of miR-4443 increased the radiosensitivity of ESCC cells. Notably, miR-4443 modulated radiosensitivity by influencing DNA damage repair, apoptosis, and G2 cycle arrest. By using WGCNA and experimental validation, we identified PTPRJ as a key target for miRNA-4443 to regulate radiosensitivity. The effects of miR-4443 overexpression or inhibition could be reversed by increasing or decreasing PTPRJ expression.ConclusionIn this study, miR-4443 is found to promote radiotherapy resistance in ESCC cells by regulating PTPRJ expression, which provides a new perspective and clue to alleviate radioresistance.

【 授权许可】

CC BY   
© The Author(s) 2022

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