MicroRNA-139-5p inhibits bladder cancer proliferation and self-renewal by targeting the Bmi1 oncogene
MicroRNA-139-5p inhibits bladder cancer proliferation and self-renewal by targeting the Bmi1 oncogene
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MicroRNA-139-5p 通过靶向 Bmi1 癌基因抑制膀胱癌增殖和自我更新
DOI：
10.1177/1010428317718414
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发表时间：
2017-07-18
期刊：
影响因子：
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通讯作者：
Xu, Chuanrui
中科院分区：
文献类型：
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作者：
Luo, Hongbo;Yang, Rui;Xu, Chuanrui
据报道，MiR-139-5p 在多种癌症中过度表达，但其在膀胱癌中的作用尚未阐明。在此，我们报道 miR-139-5p 在膀胱癌中发挥肿瘤抑制因子的作用，并通过直接靶向 Bmi1 来抑制癌症干细胞的自我更新。我们发现，与癌旁正常组织相比，膀胱癌标本中 miR-139-5p 的表达显着下调。在体外，恢复 miR-139-5p 表达可显着抑制膀胱癌细胞的增殖。机制分析表明，miR-139-5p可以通过与Bmi1信使RNA的3'非翻译区结合来降低Bmi1蛋白水平。膀胱癌细胞中 miR-139-5p 的恢复可抑制干细胞相关蛋白（如 c-MYC、NANOG、OCT4 和 KLF4）以及信号通路（如 Wnt 信号传导）。此外，miR-139-5p的表达还通过抑制Bmi1来阻断膀胱癌干细胞的自我更新。总之，我们的研究支持 miR-139-5p 在膀胱癌发展中充当肿瘤抑制因子，并抑制膀胱癌的癌症干细胞特性。我们的研究还表明 miR-139-5p 有潜力用作膀胱癌治疗的治疗分子。
MiR-139-5p has been reported to be overexpressed in many types of cancers, but its role in bladder cancer has not been elucidated yet. Here, we report that miR-139-5p functions as a tumor suppressor in bladder cancer and inhibits the cancer stem cell self-renewal by targeting Bmi1 directly. We found that miR-139-5p expression was significantly downregulated in the bladder cancer specimens compared with that in adjacent normal tissues. In vitro, restoration of miR-139-5p expression significantly inhibited the proliferation of bladder cancer cells. Mechanism analysis revealed that miR-139-5p could decrease Bmi1 protein levels by binding to the 3′ untranslated region of Bmi1 messenger RNA. Stem cell–related proteins such as c-MYC, NANOG, OCT4, and KLF4 and signaling pathways such as Wnt signaling were suppressed by restoration of miR-139-5p in bladder cancer cells. In addition, miR-139-5p expression also blocked self-renewal of bladder cancer stem cells by inhibiting Bmi1. In summary, our study supports that miR-139-5p acts as a tumor suppressor in bladder cancer development and suppresses cancer stem cell property of bladder cancer. Our study also suggests that miR-139-5p has the potential to be used as a therapeutic molecule for bladder cancer treatment.