MicroRNA-298 determines the radio-resistance of colorectal cancer cells by directly targeting human dual-specificity tyrosine(Y)-regulated kinase 1A  

作　　者：Mei-Zhu Shen Yong Zhang Fang Wu Mei-Zhen Shen Jun-Lin Liang Xiao-Long Zhang Xiao-Jian Liu Xin-Shu Li Ren-Sheng Wang 

机构地区：[1]Department of Radiotherapy,The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,Guangxi Zhuang Autonomous Region,China [2]Department of Radiotherapy,People’s Hospital of Guangxi Zhuang Autonomous Region,Nanning 530021,Guangxi Zhuang Autonomous Region,China [3]Department of Colorectal Anal Surgery,The First Affiliated Hospital of Guangxi Medical University,Nanning 530021,Guangxi Zhuang Autonomous Region,China [4]Department of Clinical Medicine,Guangxi Medical University,Nanning 530021,Guangxi Zhuang Autonomous Region,China

出　　处：《World Journal of Gastrointestinal Oncology》2024年第4期1453-1464,共12页世界胃肠肿瘤学杂志（英文版）（电子版）

基　　金：This study was reviewed and approved by the Experimental Animal Ethics Committee of the First Affiliated Hospital of Guangxi Medical University(Approval No.2023-E386-01).

摘　　要：BACKGROUND Radiotherapy stands as a promising therapeutic modality for colorectal cancer(CRC);yet,the formidable challenge posed by radio-resistance significantly undermines its efficacy in achieving CRC remission.AIM To elucidate the role played by microRNA-298(miR-298)in CRC radio-resistance.METHODS To establish a radio-resistant CRC cell line,HT-29 cells underwent exposure to 5 gray ionizing radiation that was followed by a 7-d recovery period.The quantification of miR-298 levels within CRC cells was conducted through quantitative RT-PCR,and protein expression determination was realized through Western blotting.Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and proliferation by clonogenic assay.Radio-induced apoptosis was discerned through flow cytometry analysis.RESULTS We observed a marked upregulation of miR-298 in radio-resistant CRC cells.MiR-298 emerged as a key determinant of cell survival following radiation exposure,as its overexpression led to a notable reduction in radiation-induced apoptosis.Intriguingly,miR-298 expression exhibited a strong correlation with CRC cell viability.Further investigation unveiled human dual-specificity tyrosine(Y)-regulated kinase 1A(DYRK1A)as miR-298’s direct target.CONCLUSION Taken together,our findings underline the role played by miR-298 in bolstering radio-resistance in CRC cells by means of DYRK1A downregulation,thereby positioning miR-298 as a promising candidate for mitigating radioresistance in CRC.

关 键 词：MicroRNA-298 Human dual-specificity tyrosine(Y)-regulated kinase 1A Colorectal cancer Radio-resistance p53 binding protein 1 

分 类 号：R735.34[医药卫生—肿瘤]