Down-regulation of LncRNA TUG1 enhances radiosensitivity in bladder cancer via suppressing HMGB1 expression.
Down-regulation of LncRNA TUG1 enhances radiosensitivity in bladder cancer via suppressing HMGB1 expression.
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DOI：
10.1186/s13014-017-0802-3
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发表时间：
2017-04-04
期刊：
影响因子：
--
通讯作者：
Li W
中科院分区：
文献类型：
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作者：
Jiang H;Hu X;Zhang H;Li W
长链非编码RNA（lncRNA）已被报道可调节不同癌细胞对放化疗的敏感性。lncRNA牛磺酸上调基因1（TUG 1）的异常表达与膀胱癌的发生发展有关，但其在膀胱癌放射抵抗中的作用及机制尚不清楚。实时定量PCR（qRT-PCR）检测膀胱癌组织和细胞株中TUG 1和HMGB 1 mRNA的表达。通过蛋白质印迹试验检测HMGB 1蛋白水平。采用不同剂量的X射线对膀胱癌细胞进行放射治疗。克隆形成实验检测克隆存活率，CCK-8试剂盒检测细胞活力。流式细胞仪检测各组细胞凋亡情况。建立小鼠移植瘤模型，观察TUG 1对肿瘤生长的影响。TUG 1和HMGB 1在膀胱癌组织和细胞系中的表达均显著升高。放射治疗后TUG 1和HMGB 1的表达明显升高。TUG 1基因敲除可抑制SW 780和BIU 87细胞在辐射下的增殖，促进细胞凋亡，降低集落存活率。此外，TUG 1缺失抑制了HMGB 1 mRNA和蛋白水平。此外，在膀胱癌细胞中，HMGB 1的过表达逆转了TUG 1敲除诱导的效应。放射治疗显著降低了异种移植模型中的肿瘤体积和重量，当与TUG 1沉默联合时，这种作用更明显。LncRNA TUG 1基因敲除通过抑制HMGB 1表达增强膀胱癌放射敏感性TUG 1是膀胱癌放射抵抗的潜在调节因子，有望成为膀胱癌治疗的靶点。
Long non-coding RNAs (lncRNAs) have been reported to regulate the sensitivity of different cancer cells to chemoradiotherapy. Aberrant expression of lncRNA Taurine-upregulated gene 1 (TUG1) has been found to be involved in the development of bladder cancer, however, its function and underlying mechanism in the radioresistance of bladder cancer remains unclear. Quantitative real-time PCR (qRT-PCR) was conducted to measure the expression of TUG1 and HMGB1 mRNA in bladder cancer tissues and cell lines. HMGB1 protein levels were tested by western blot assays. Different doses of X-ray were used for radiation treatment of bladder cancer cells. Colony survival and cell viability were detected by clonogenic assay and CCK-8 Kit, respectively. Cell apoptosis was determined by flow cytometry. A xenograft mouse model was constructed to observe the effect of TUG1 on tumor growth in vivo. The levels of TUG1 and HMGB1 were remarkably increased in bladder cancer tissues and cell lines. Radiation treatment markedly elevated the expression of TUG1 and HMGB1. TUG1 knockdown inhibited cell proliferation, promoted cell apoptosis and decreased colony survival in SW780 and BIU87 cells under radiation. Moreover, TUG1 depletion suppressed the HMGB1 mRNA and protein levels. Furthermore, overexpression of HMGB1 reversed TUG1 knockdown-induced effect in bladder cancer cells. Radiation treatment dramatically reduced the tumor volume and weight in xenograft model, and this effect was more obvious when combined with TUG1 silencing. LncRNA TUG1 knockdown enhances radiosensitivity of bladder cancer by suppressing HMGB1 expression. TUG1 acts as a potential regulator of radioresistance of bladder cancer, and it may represent a promising therapeutic target for bladder cancer patients.