Haider Romain, Massa Fabienne, Kaminski Lisa, Clavel Stephan, Djabari Zied, Robert Guillaume, Laurent Kathiane, Michiels Jean-François, Durand Matthieu, Ricci Jean-Ehrland, Tanti Jean-François, Bost Frédéric, Ambrosetti Damien
Université Côte d'Azur, C3M-Inserm U1065, Nice, France.
Urology Department, CHU Nice, Nice, France.
Oncotarget. 2017 Aug 24;8(44):77309-77316. doi: 10.18632/oncotarget.20468. eCollection 2017 Sep 29.
Predictive biomarkers for advanced prostate cancer (PCa) are still missing. The sirtuin 7 (SIRT7) has been linked to tumorogenesis but its role in prostate cancer is poorly documented. To determine if SIRT7 can be a biomarker for aggressive prostate cancer and plays a role in PCa aggressiveness. We analyzed the expression of SIRT7 by immunohistochemistry in 57 patients comparing healthy with adjacent cancer tissue. SIRT7 levels were significantly elevated in tumors and its expression was positively associated with the grade. We also demonstrated that the knock down of SIRT7 decreased the migration of DU145 and PC3 cells (two androgen-independent prostate cancer cell lines) whereas the overexpression of the native protein but not the mutated form increased the cell migration and the invasion of the poorly aggressive prostate cancer cell line LNCaP. Finally, we also showed that SIRT7 overexpression induced the resistance to docetaxel. Our results demonstrate that SIRT7 promotes prostate cancer cell aggressiveness and chemoresistance and suggest that SIRT7 is a good predictive biomarker of PCa aggressiveness.
晚期前列腺癌(PCa)的预测性生物标志物仍然缺失。沉默调节蛋白7(SIRT7)与肿瘤发生有关,但其在前列腺癌中的作用鲜有文献记载。为了确定SIRT7是否可作为侵袭性前列腺癌的生物标志物并在PCa侵袭性中发挥作用。我们通过免疫组织化学分析了57例患者中SIRT7的表达情况,并将健康组织与相邻癌组织进行了比较。肿瘤中SIRT7水平显著升高,其表达与分级呈正相关。我们还证明,敲低SIRT7可降低DU145和PC3细胞(两种雄激素非依赖性前列腺癌细胞系)的迁移,而天然蛋白而非突变形式的过表达则增加了低侵袭性前列腺癌细胞系LNCaP的细胞迁移和侵袭。最后,我们还表明SIRT7过表达诱导了对多西他赛的耐药性。我们的结果表明,SIRT7促进前列腺癌细胞的侵袭性和化疗耐药性,并提示SIRT7是PCa侵袭性的良好预测生物标志物。