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Cytokeratin 13 promotes radiotherapy sensitivity of nasopharyngeal carcinoma by downregulating the MEK/ERK pathway

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机构: [1]Department of Otorhinolaryngology, Head and Neck Surgery, The Affiliated Hospital of Yunnan University, the Second People's Hospital of Yunnan Province, Yunnan Eye Hospital, Kunming, China.
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关键词: CDK4/CDK6 cytokeratin 13 MEK/ERK nasopharyngeal carcinoma radioresistance

摘要:
Radiation therapy is the first treatment choice for nasopharyngeal carcinoma (NPC), while radiation resistance and recurrence have become the primary factors and are associated with poor prognosis in the clinical treatment of NPC patients. The purpose of the present study was to explore the sensitivity and molecular basis of cytokeratin 13 (CK13) that regulates NPC radiotherapy.HNE-3 or C666-1 cell line was used for overexpression and knockdown tests. Under radiotherapy conditions, CCK-8 assay, clone formation assay, and flow cytometry analyzed the effects of CK13 overexpression on cell proliferation, apoptosis, and cell cycle, respectively. In addition, Western blotting detected CK13-mediated downregulation of cell cycle-related genes. The mouse subcutaneous tumor-bearing experiment identified the effects of CK13 overexpression on the treatment of NPC in vivo. Further, Western blotting, CCK-8 assay, and flow cytometry investigated whether the CK13-mediated cell apoptosis involves the MEK/ERK signaling pathway.Overexpression of CK13 significantly inhibited the survival of HNE-3 cells under radiotherapy in vitro and in vivo, and there was a substantial decrease in cyclin-dependent kinase 4 and 6 (CDK4/6) levels promoting the cell percentage number in the G2/M phase and, subsequently, the ratio of the apoptotic cells. In contrast, the knockdown of CK13 showed the opposite partial regulatory effect. Interestingly, CK13 overexpression also showed a reduction in the survival of C666-1 cells and an increased ratio of the apoptotic cells under radiotherapy treatment. Furthermore, higher levels of CK13 downregulated the MEK/ERK signaling pathway, resulting in decreased HNE-3 cell proliferation and increased apoptosis. However, ERK activators were able to rescue the process partially.Together, these results showed that CK13 promoted the radiosensitivity of NPC cells by downregulating the MEK/ERK signaling pathway. Thus, targeting CK13 provided insights into the treatment of NPC radiotherapy.© 2022 International Union of Biochemistry and Molecular Biology.

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出版当年[2022]版:
大类 | 3 区 生物学
小类 | 3 区 生化与分子生物学 4 区 细胞生物学
最新[2023]版:
大类 | 3 区 生物学
小类 | 3 区 生化与分子生物学 4 区 细胞生物学
第一作者:
第一作者机构: [1]Department of Otorhinolaryngology, Head and Neck Surgery, The Affiliated Hospital of Yunnan University, the Second People's Hospital of Yunnan Province, Yunnan Eye Hospital, Kunming, China.
通讯作者:
通讯机构: [1]Department of Otorhinolaryngology, Head and Neck Surgery, The Affiliated Hospital of Yunnan University, the Second People's Hospital of Yunnan Province, Yunnan Eye Hospital, Kunming, China. [*1]Department of Otorhinolaryngology, Head and Neck Surgery, the Affiliated Hospital of Yunnan University, the Second People's Hospital of Yunnan Province, Yunnan Eye Hospital, No. 176 Qingnian Road, Kunming 650021, Yunnan, P.R. China.
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