The miR-193a-3p-regulated ING5 gene activates the DNA damage response pathway and inhibits multi-chemoresistance in bladder cancer.
The miR-193a-3p-regulated ING5 gene activates the DNA damage response pathway and inhibits multi-chemoresistance in bladder cancer.
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miR-193a-3p调节的ING5基因激活DNA损伤反应途径并抑制膀胱癌的多重化疗耐药性
DOI：
10.18632/oncotarget.3555
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发表时间：
2015-04-30
期刊：
影响因子：
--
通讯作者：
Zhu J
中科院分区：
文献类型：
--
作者：
Li Y;Deng H;Lv L;Zhang C;Qian L;Xiao J;Zhao W;Liu Q;Zhang D;Wang Y;Yan J;Zhang H;He Y;Zhu J
作为治愈性癌症化疗的主要障碍，化疗耐药性对癌症研究人员和临床医生都提出了巨大的挑战。我们之前已经表明，膀胱癌（BCa）细胞系 5637 对五种化疗药物的细胞毒性明显比 H-bc 细胞更敏感。通过基于 RNA-seq 的组学分析和 mRNA 和蛋白质水平的验证，我们发现与 H-bc 细胞相比，生长抑制剂 5 (ING5) 基因在 5637 细胞中表达上调，表明它在 BCa 化疗耐药中具有抑制作用。 siRNA 介导的 ING5 抑制增加了 5637 细胞的化疗耐药性并抑制了 DNA 损伤反应途径。相反，EGFP-ING5的强制表达降低了H-bc细胞的化疗耐药性并激活了DNA损伤反应途径。我们还表明，ING5 基因表达受到 miR-193a-3p 的抑制，并且有助于 miR-193a-3p 在激活 BCa 化疗耐药中的作用。我们的结果证明了 ING5 抑制 BCa 化疗耐药性的作用和机制。
As the major barrier to curative cancer chemotherapy, chemoresistance presents a formidable challenge to both cancer researchers and clinicians. We have previously shown that the bladder cancer (BCa) cell line 5637 is significantly more sensitive to the cytoxicity of five chemotherapeutic agents than H-bc cells. Using an RNA-seq-based omic analysis and validation at both the mRNA and protein levels, we found that the inhibitor of growth 5 (ING5) gene was upregulated in 5637 cells compared with H-bc cells, indicating that it has an inhibitory role in BCa chemoresistance. siRNA-mediated inhibition of ING5 increased the chemoresistance and inhibited the DNA damage response pathway in 5637 cells. Conversely, forced expression of EGFP-ING5 decreased the chemoresistance of and activated the DNA damage response pathway in H-bc cells. We also showed that ING5 gene expression is inhibited by miR-193a-3p and is instrumental in miR-193a-3p's role in activating BCa chemoresistance. Our results demonstrate both the role and mechanism of inhibition of BCa chemoresistance by ING5.
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影响因子：
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作者：
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