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LINC-PINT impedes DNA repair and enhances radiotherapeutic response by targeting DNA-PKcs in nasopharyngeal cancer.

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机构： [1]Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008 Changsha, P. R. China. [2]Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, 410008 Changsha, P. R. China. [3]Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, 410008 Changsha, P. R. China. [4]National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, 410008 Changsha, Hunan, P. R. China. [5]The Third Xiangya Hospital of Central South University, Central South University, 138 Tongzipo Road, 410013 Changsha, P. R. China. [6]Department of Laboratory Medicine, National Key Laboratory of Biotherapy/ Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, 610000 Chengdu, P. R. China. [7]Department of Gynaecology and Obstetrics, The Second Xiangya Hospital of Central South University, Central South University, 410008 Changsha, P. R. China. [8]The First Affiliated Hospital of Guangdong Pharmaceutical University, 510060 Guangzhou, P. R. China. [9]Shenzhen Center for Chronic Disease Control and Prevention, Shenzhen, 518020 Guangdong, P. R. China

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Radioresistance continues to be the leading cause of recurrence and metastasis in nasopharyngeal cancer. Long noncoding RNAs are emerging as regulators of DNA damage and radioresistance. LINC-PINT was originally identified as a tumor suppressor in various cancers. In this study, LINC-PINT was significantly downregulated in nasopharyngeal cancer tissues than in rhinitis tissues, and low LINC-PINT expressions showed poorer prognosis in patients who received radiotherapy. We further identified a functional role of LINC-PINT in inhibiting the malignant phenotypes and sensitizing cancer cells to irradiation in vitro and in vivo. Mechanistically, LINC-PINT was responsive to DNA damage, inhibiting DNA damage repair through ATM/ATR-Chk1/Chk2 signaling pathways. Moreover, LINC-PINT increased radiosensitivity by interacting with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and negatively regulated the expression and recruitment of DNA-PKcs. Therefore, these findings collectively support the possibility that LINC-PINT serves as an attractive target to overcome radioresistance in NPC.

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出版当年[2021]版：

大类 | 1 区

生物学

小类 | 2 区细胞生物学

最新[2023]版：

大类 | 1 区

生物学

小类 | 2 区细胞生物学

第一作者：

第一作者机构： [1]Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008 Changsha, P. R. China. [2]Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, 410008 Changsha, P. R. China. [3]Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, 410008 Changsha, P. R. China. [4]National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, 410008 Changsha, Hunan, P. R. China.

通讯作者：

通讯机构： [1]Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 87 Xiangya Road, 410008 Changsha, P. R. China. [2]Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, 110 Xiangya Road, 410008 Changsha, P. R. China. [3]Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, 110 Xiangya Road, 410008 Changsha, P. R. China. [4]National Clinical Research Center for Geriatric Disorders, 87 Xiangya Road, 410008 Changsha, Hunan, P. R. China.

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