LncRNA UCA1 靶向 miR-520a-5p 对膀胱癌细胞增殖、凋亡及放射敏感性的影响
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1.宜昌市中心人民医院泌尿外科,湖北 宜昌 443000;2.武汉市第三医院泌尿外科,武汉 430000

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R737. 14;R730. 55;R-33

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Effects of LncRNA UCA1 on proliferation, apoptosis and radiosensitivity of bladder cancer cells by targeting miR-520a-5p
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1. Department of Urology, Yichang Central People’s Hospital, Yichang 443000, China.2. Department of Urology, Wuhan Third Hospital, Wuhan 430000

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    摘要:

    目的 探讨长链非编码核糖核酸尿路上皮癌胚抗原 1(LncRNA UCA1)调节 miR-520a-5p 对膀胱癌细胞增殖、凋亡及放疗敏感性的影响。 方法 RT-qPCR 检测正常膀胱上皮细胞株(HCV-29)和人膀胱癌细胞株(SW780、HT1376、BIU87 和 T24)LncRNA UCA1、miR-520a-5p 表达,使用不同放疗剂量(0 ~ 8 Gy)处理T24 细胞,检测细胞增殖活性,将 T24 细胞分为对照(Control)组、sh-NC 组、sh-UCA1 组、sh-UCA1+anti-miR-NC组和 sh-UCA1+anti-miR-520a-5p 组,各组细胞使用放疗剂量 2 Gy 处理,分别检测各组细胞增殖凋亡及细胞周期蛋白 D1(CyclinD1)、Ki-67 抗原(Ki-67)、Bcl-2 相关 X 蛋白(Bax)、胱天蛋白酶-3(Caspase-3)蛋白表达;双荧光素酶报告基因实验、原位杂交(FISH)实验、RNA 免疫共沉淀实验验证 LncRNA UCA1 与 miR-520a-5p 的靶向关系。 建立裸鼠肿瘤异种移植模型,验证 LncRNA UCA1 对膀胱癌放疗敏感性的影响。 结果 在膀胱癌细胞系中 LncRNA UCA1 表达升高,miR-520a-5p 表达降低(P<0. 05);不同放疗剂量(0~ 8 Gy)处理 T24 细胞后,随着放射剂量增加,sh-UCA1 组细胞增殖活性明显低于 sh-NC 组(P<0. 05);选择 2 Gy 放疗剂量处理 T24 细胞。 在 T24 细胞中,敲低 LncRNA UCA1 可显著抑制细胞增殖,促进细胞凋亡并增加放疗敏感性,下调CyclinD1、Ki-67 表达,上调 Bax、Caspase-3 表达(P<0. 05);miR-520a-5p 拮抗剂可减弱敲低 LncRNA UCA1 对膀胱癌细胞增殖、凋亡及放疗敏感性的影响(P<0. 05);LncRNA UCA1 可靶向负调控 miR-520a-5p 表达。 敲低LncRNA UCA1 联合放疗可显著抑制膀胱癌移植瘤生长,增加放疗敏感性(P<0. 05)。 结论 LncRNA UCA1在膀胱癌细胞中表达上调,敲低 LncRNA UCA1 可通过上调 miR-520a-5p 表达,抑制细胞增殖并诱导细胞凋亡,增强膀胱癌细胞放疗敏感性。

    Abstract:

    Objective To investigate the effects of urothelial carcinoma antigen 1 long non-coding RNA(LncRNA UCA1) on the proliferation, apoptosis, and radiosensitivity of bladder cancer cells by regulating miR-520a-5p. Methods LncRNA UCA1 and miR-520a-5p were detected in normal bladder epithelial (HCV-29) and human bladder cancer (SW780, HT1376, BIU87 and T24) cell lines by quantitative reverse transcription-polymerase chain reaction. T24 cells were treated with different radiation doses (0~8 Gy) and cell proliferation activity was detected.T24 cells were assigned to Control, sh-NC, sh-UCA1, sh-UCA1 + anti-miR-NC, and sh-UCA1 + anti-miR-520a-5p groups. Cells in each group were treated with a radiation dose of 2 Gy, and cell proliferation, apoptosis, and cyclin D1, Ki-67, Bax, and Caspase-3 protein expression levels were detected. The targeting relationship between LncRNA UCA1 and miR-520a-5p was verified by dual-luciferase reporter gene, fluorescence in situ hybridization, and RNA immunoprecipitation assays. A nude mouse tumor xenotransplantation model was established, and the effect of LncRNA UCA1 on the radiosensitivity of bladder cancer was verified. Results LncRNA UCA1 was increased and miR-520a-5p was decreased in bladder cancer cell lines. Treating T24 cells with different radiation doses (0~8 Gy) reduced cell proliferation activity in the sh-UCA1 group compared with the sh-NC group, in line with increasing radiation dose (P<0. 05). T24 cells and a radiation dose of 2 Gy were therefore selected for subsequent experiments. Knockdown of LncRNA UCA1 in T24 cells inhibited cell proliferation, promoted cell apoptosis, increased radiosensitivity, down-regulated cyclin D1 and Ki-67, and upregulated Bax and Caspase-3 (P<0. 05). miR-520a-5p antagonist weakened the impacts of LncRNA UCA1 knockdown on the proliferation, apoptosis, and radiosensitivity of bladder cancer cells (P<0. 05). LncRNA UCA1 targeted the negative regulation of miR-520a-5p. Knockdown of LncRNA UCA1 combined with radiotherapy inhibited the growth of bladder cancer tumor transplants and increased their radiosensitivity (P<0. 05). Conclusions LncRNA UCA1 is up-regulated in bladder cancer cells. Knockdown of LncRNA UCA1 can inhibit cell proliferation, induce apoptosis, and enhance the radiosensitivity of bladder cancer cells by up-regulating miR-520a-5p.

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余 洋,熊 飞,陈晓波,孙 伟,张 炜. LncRNA UCA1 靶向 miR-520a-5p 对膀胱癌细胞增殖、凋亡及放射敏感性的影响[J].中国比较医学杂志,2026,36(8):61~70.

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  • 收稿日期:2025-07-15
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  • 在线发布日期: 2026-06-17
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