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Increased chemo-sensitivity by knockdown coilin expression involved acceleration of premature cellular senescence in HeLa cells

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机构: [1]Capital Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing, Peoples R China; [2]Capital Med Univ, Inst Canc, Beijing Key Lab Tumor Invas & Metastasis Res, Beijing, Peoples R China; [3]Capital Med Univ, Beijing Childrens Hosp, Hematol Oncol Ctr, Beijing, Peoples R China; [4]Beijing Inst Brain Disorders, Beijing, Peoples R China; [5]Capital Med Univ, Dept Biochem & Mol Biol, Beijing 100069, Peoples R China
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关键词: Cajal body Coilin Cisplatin Senescence SA-beta-gal

摘要:
Coilin is a marker protein of the Cajal body (CB). Cajal bodies, functional nuclear structure, play important roles for the maturation of telomerase mRNAs. However, whether CB participates in the process of cell senescence is unknown. Cisplatin is a frequently used drug for the chemotherapy for various cancers, which was recently reported to be able to induce premature senescence of tumor cells. In this study, we found that when HeLa cells were treated with 2 mu g/ml cisplatin for 4 days, stagnant cell growth, especially in cells stained positive of SA-beta-gal, was accompanied with significant changes in CB morphologies. The removal of cisplatin allowed the recovery of normal CB appearance, but was not able to restore cells from senescent states. Knocking down coilin expression by siRNA attenuated the growth and reduced the viability of treated cells, and the decreased rate of CB formation correlated with increased staining of SA 0 beta-gal. Interestingly, when coilin knocked-down cells exposed to cisplatin, the drug sensitivity as shown by the reduction of cell viability was significantly increased compared to the control siRNA transfection groups. Overexpression of coilin phosphomutants increased SA-beta-gal fluorescence following treatments with cisplatin as compared to the wild type coilin transfection. Our results indicated that coilin was an important functional player that involved in cisplatin-induced premature cell senescence. It suggested that the modulation of coilin expression could be considered as a potential anti-tumor strategy to increase the sensitivity of chemotherapy through which drug-induced cell senescence was accelerated. (C) 2017 Elsevier Inc. All rights reserved.

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出版当年[2016]版:
大类 | 3 区 生物
小类 | 4 区 生化与分子生物学 4 区 生物物理
最新[2023]版:
大类 | 3 区 生物学
小类 | 3 区 生物物理 4 区 生化与分子生物学
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出版当年[2015]版:
Q2 BIOPHYSICS Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版:
Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Q3 BIOPHYSICS

影响因子: 最新[2023版] 最新五年平均 出版当年[2015版] 出版当年五年平均 出版前一年[2014版] 出版后一年[2016版]

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第一作者机构: [1]Capital Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing, Peoples R China;
通讯作者:
通讯机构: [1]Capital Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing, Peoples R China; [2]Capital Med Univ, Inst Canc, Beijing Key Lab Tumor Invas & Metastasis Res, Beijing, Peoples R China; [4]Beijing Inst Brain Disorders, Beijing, Peoples R China; [5]Capital Med Univ, Dept Biochem & Mol Biol, Beijing 100069, Peoples R China
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