基因敲除
下调和上调
DNA损伤
细胞生长
癌症研究
化学
流式细胞术
端粒
细胞生物学
分子生物学
生物
细胞凋亡
DNA
基因
生物化学
作者
Fang Li,Jilin Wen,Xiaowu Zhong,Chuanli Gao,Miyuan Yang,Maoju Tang,Zichun Yuan,Qin Wang,Xu Liu,Qiang Ma,Xiaolan Guo
标识
DOI:10.1615/critreveukaryotgeneexpr.2023048720
摘要
TPP1, as one of the telomere-protective protein complex, functions to maintain telomere stability. In this study, we found that TPP1 was significantly upregulated in esophageal cancer (EC). We found that the proliferation and migration ability were significantly inhibited, while the results of flow cytometry assay indicated that the growth was hindered in the G1 phase after TPP1 knockdown. However, the proliferative viability and migratory ability were reversed after TPP1 overexpression in EC cells. Then, we found a significant increase in β-galactosidase positivity following TPP1 knockdown and the opposite following TPP1 overexpression in EC cells. Furthermore, TPP1 knockdown increased DNA damage and upregulated expression of the γ-H2AXS139 in the cell nucleus. Correspondingly, DNA damage was reversed after TPP1 overexpression in EC cells. Similarly, we found that the expression of ATM/ATR pathway proteins were upregulated after TPP1 knockdown, while the expression of the above proteins was downregulated after TPP1 overexpression in EC cells. TPP1 knockdown significantly inhibited the growth of transplanted tumors and upregulated the expression of ATM/ATR pathway proteins in transplanted tissues, whereas TPP1 overexpression significantly promoted their proliferation and downregulated the expression of the above proteins in vivo. Strikingly, we found that TPP1 could reduce the chemosensitivity of EC cells to cisplatin, which may have a potential link to clinical chemoresistance. In conclusion, TPP1 regulates the DNA damage response through the ATM/ATR-p53 signaling pathway and chemoresistance and may be a new target for improving the efficacy of chemotherapy in the treatment of EC.
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