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XPC蛋白促进膀胱癌细胞DNA损伤修复的作用 被引量:4

XPC protein promotes UV DNA damage response of human bladder cancer cells
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摘要 目的探讨着色性干皮病基因C(xeroderma pigmentosum group C,XPC)对膀胱癌T24细胞紫外线(ultraviolet ray,UV)介导的DNA损伤修复的作用及机制。方法利用shRNA策略,Western blot鉴定XPC沉默效果,建立稳定抑制XPC的膀胱肿瘤T24细胞模型;CCK-8法检测UV对细胞增殖的影响;宿主反应实验检测细胞DNA损伤修复能力的差异;免疫荧光检测UV损伤处理、XPC干扰前后p-ATM蛋白分子向细胞核DNA损伤部位募集情况。结果成功建立稳定抑制XPC的膀胱肿瘤T24细胞模型,干扰XPC后,细胞对UV损伤敏感性出现显著差异(P<0.01),干扰组DNA损伤修复能力较对照组降低(P<0.01),p-ATM向损伤区域的募集作用降低(P<0.01)。结论 UV损伤条件下,膀胱癌T24细胞通过XPC介导p-ATM向损伤区域的募集,以降低细胞UV损伤修复能力。 Objective To determine the role and the underlying mechanisms of xeroderma pigmentosum group C (XPC) in ultraviolet (UV) DNA damage response of human bladder cancer cell line T24. Methods XPC siRNA was used to induce T24 cells with stable XPC knockdown, and the obtained cells were confirmed by Western blotting. CCK-8 kit was employed to detect the inhibitory effects of UV on the T24 cells and T24 cells with XPC knockdown. The ability of DNA repair was evaluated by host-cell reactivation (HCR) assay. The nuclear recruitment of p-ATM towards the damaged DNA was determined by immunofluoresence staining. Results The T24 cells with stable XPC knockdown were successfully established. Compared to the normal T24 cells, the XPC knockdown cells were more sensitive to UV treatment (P〈0.01), showed declined ability of DNA repair (P〈0.01), and reduced nuclear concentration of p-ATM towards the damaged DNA(P〈0.01). Conclusion XPC play a major role in DNA repair via affecting the nuclear recruitment of p-ATM in T24 cells.
出处 《第三军医大学学报》 CAS CSCD 北大核心 2014年第9期856-859,共4页 Journal of Third Military Medical University
基金 国家自然科学基金面上项目(30972979)~~
关键词 着色性干皮病基因C 膀胱癌 DNA损伤 紫外线 p—ATM xeroderma pigmentosum group C bladder cancer DNA damage ultraviolet rays p-ATM
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参考文献13

  • 1Tian K, Rajendran R, Doddananjaiah M, et al. Dynamics of DNA damage induced pathways to cancer [ J ]. PLoS One, 2013, 8 (9) : e72303.
  • 2Scharer O D. Nucleotide excision repair in eukaryotes[ J ]. Cold Spring Harb Perspeet Biol, 2015, 5(10) : a012609.
  • 3Shiloh Y, Ziv Y. The ATM protein kinase: regulating the cellular re- sponse to genotoxic stress, and more [J] Nat Rev Mol Cell Biol, 2013, 14(4): 197-210.
  • 4Renaud E, Miccoli L, Zacal N, et al. Differential contribution of XPC, RAD23A, RAD23B and CENTRIN 2 to the UV-response in hu- man cells[ J ]. DNA Repair ( Amst), 2011, 10 (8) : 835 - 847.
  • 5Lans H, Marteijn J A, Schumacher B, et al. Involvement of global ge- nome repair, transcription coupled repair, and chromatin remodeling in UV DNA damage response changes during development [ J ]. PLoSGenet, 2010, 6(5): e1000941.
  • 6Sugasawa K. XPC: its product and biological roles[J]. Adv Exp Med Biol, 2008, 637 : 47 - 56.
  • 7Chen Z, Yang J, Wang G, et al. Attenuated expression of xeroderma pigmentosum group C is associated with critical events in human blad- der cancer carcinogenesis and progression[ J]. Cancer Res, 2007, 67 (10) : 4578 -4585.
  • 8Wang G, Chuang L, Zhang X, et al. The initiative role of XPC protein in eisplatin DNA damaging treatment-mediated cell cycle regulation [J]. Nucleic Acids Res, 2004, 32(7) : 2231 -2240.
  • 9Xu Y, Xu C, Price B D. Mechanistic links between ATM and histone methylation codes during DNA repair [ J ]. Prog Mol Biol Transl Sei, 2012, 110:263-288.
  • 10Johnson N, Cai D, Kennedy R D, et al. Cdkl participates in BRCAl-dependent S phase checkpoint control in response to DNA damage [ J]. Mol Cell, 2009, 35 (3) : 327 - 339.

同被引文献39

  • 1Wang S,Xue S,Dai Y,et al.Reduced expression of microRNA-100 confers unfavorable prognosis in patients with bladder cancer[J].Diagn Pathol,2012,7:159.
  • 2Lee J Y,Joo H J,Cho D S,et al.Prognostic significance of substaging according to the depth of lamina propria invasion in primary T1 transitional cell carcinoma of the bladder[J].Korean J Urol,2012,53:317.
  • 3van Rhijn B W,Burger M,Lotan Y,et al.Recurrence and progression of disease in non-muscle-invasive bladder cancer:from epidemiology to treatment strategy[J].Eur Urol,2009,56:430.
  • 4Fujii Y,Fukui I,Kihara K,et al.Significance of bladder neck involvement on progression in superficial bladder cancer[J].Eur Urol,1998,33:464.
  • 5Haleblian G E,Skinner E C,Dickinson M G,et al.Hydronephrosis as a prognostic indicator in bladder cancer patients[J].J Urol,1998,160:2011.
  • 6Rodriguez-Aloson A,Pit a-f ernandez S,Gonzalez-Carrero J,et al.Mult-I variate analysis of survival,recurrence,progression and development of metastasis in T1 and T2a transit ional cell bladder carcinoma[J].Cancer,2002,94:1677.
  • 7Millán-Rodríguez F,Chéchile-Toniolo G,Salvador-Bayarri J,et al.Multivariate analysis of the prognostic factors of primary superficial bladder cancer[J].J Urol,2000,163:73.
  • 8Czarny P, Pawlowska E, Bialkowska-Warzecha J, et al. Au- tophagy in DNA damage response[ J]. Int J Mol Sci, 2015, 16(2) : 2641 -2662. DOI: 10.3390/ijms16022641.
  • 9Qiang L, Zhao B, Shah P, et al. Autophagy positively regu- lates DNA damage recognition by nucleotide excision repair [J]. Autophagy, 2016, 12(2) : 357 -368. DOI: 10. 1080/ 15548627. 2015. 1110667.
  • 10Spivak G. Nucleotide excision repair in humans [ J ]. DNA Repair (Amst), 2015, 36: 13- 18. DOI: 10. 1016/j. dnarep. 2015.09. 003.

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