| 张红森,郭国营,杨 翠.MiR-152在膀胱癌中的表达以及对ERBB3/AKT2信号通路的调节作用[J].中国肿瘤,2019,28(1):55-62. |
| MiR-152在膀胱癌中的表达以及对ERBB3/AKT2信号通路的调节作用 |
| Expression of MiR-152 in Bladder Cancer and Its Effect on ERBB3/Akt Signal Pathway |
| 投稿时间：2018-09-03 |
| DOI：10.11735/j.issn.1004-0242.2019.01.A008 |
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| 中文关键词: 膀胱癌 miR-152 ERBB3/Akt信号通路 上皮—间质转化 侵袭 |
| 英文关键词:bladder cancer miR-152 ERBB3/Akt signal pathway epithelial-mesenchymal transitions invasion |
| 基金项目:国家科技重大专项（2012ZX09102301） |
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| 中文摘要: |
| 摘 要：［目的］ 探讨miR-152对ERBB3/Akt信号通路的靶向调控作用以及对膀胱癌细胞UM-UC-3增殖、侵袭和迁移活性的影响。［方法］ 收集2016年7月至2018年6月接受手术治疗的56例膀胱癌患者的肿瘤组织及相应的癌旁组织，提取总RNA，检测miR-152表达水平。体外培养UM-UC-3细胞，转染miR-152 mimics（模拟物组），同时设置空白对照组（CTL）和空转染组（NC），采用实时荧光定量聚合酶链式反应（qRT-PCR）检测miR-152的表达。采用MTT法、划痕实验和transwell小室侵袭实验观察CTL组、NC组和模拟物组细胞增殖、迁移和侵袭能力。采用双荧光素酶报告基因方法验证ERBB3与miR-152的关系。采用qRT-PCR和蛋白免疫印迹（Western blot）法检测UM-UC-3细胞中Snail、ERBB3、Akt2、p-Akt、c-myc表达量。［结果］ MiR-152在肿瘤组织中的表达量明显低于癌旁组织（P<0.05）。与膀胱上皮永生化细胞株SV-HUC-1相比，miR-152在膀胱癌细胞T24、UM-UC-3和J82中的表达量明显降低（P<0.05），其中在UM-UC-3细胞中表达量最低。经qRT-PCR法检测，模拟物组UM-UC-3细胞miR-152的表达量明显低于CTL组和NC组细胞（P<0.05）。模拟物组UM-UC-3细胞的增殖率、迁移活性以及划痕愈合率均明显低于CTL组和NC组细胞（P<0.05）。经双荧光素酶基因报告分析，ERBB3是miR-152的下游靶基因。模拟物组UM-UC-3细胞Snail、ERBB3、Akt2、p-Akt、c-myc mRNA和蛋白表达水平均低于CTL组和NC组细胞（P<0.05）。且miR-152表达量与ERBB3呈负相关性（r=-0.875，P<0.05）。［结论］ 上调miR-152可抑制ERBB3/Akt/c-myc和ERBB3/Akt/Snail信号通路的异常激活，逆转膀胱癌UM-UC-3细胞上皮—间质转化，从而降低膀胱癌生长、侵袭和迁移的风险。 |
| 英文摘要: |
| Abstract：［Purpose］ To investigate the expression of miR-152 in bladder cancer and its effect on proliferation，invasion and migration of bladder cancer cells. ［Methods］ The cancer and cancer adjacent tissue samples of 56 patients with bladder cancer were collected from July 2016 to June 2018. Quantitative real-time PCR(qRT-PCR) was used to detect miR-152 in bladder cancer tissues and cancer adjacent tissues. Bladder cancer UM-UC-3 cells were cultured in vitro and transfected with miR-152 mimics(mimics group). The proliferation，migration and invasion of UM-UC-3 cells were detected by MTT，Transwell assay and scratch test，respectively. The expression of Snail，ERBB3，Akt2，p-Akt，c-myc mRNA and proteins in UM-UC-3 cells were detected by qRT-PCR and Western blot，respectively. ［Results］ The relative expression of miR-152 in cancer tissues was lower than that in cancer adjacent tissues(P<0.05). And the miR-152 levels in bladder cancer cell lines T24，UM-UC-3 and J82 were all down-regulated compared to the human bladder epithelial SV-HUC-1 cells(P<0.05)，and the miR-152 level of UM-UC-3 cells was lowest. The miR-152 expression in UM-UC-3 cells in mimics group was higher than blank control(CTL) group and normal control(NC) group(P<0.05). The proliferation rate，migration cell number and wound healing rate of UM-UC-3 cells in mimics group were lower than those in CTL group and NC group(P<0.05). The ERBB3 was verified as a target gene of miR-152 by the dual luciferase reporter gene system. The expression of Snail，ERBB3，Akt2，p-Akt，c-myc mRNA and proteins in UM-UC-3 cells of mimics group were all lower than those in CTL group and NC group(P<0.05). And the miR-152 level in UM-UC-3 cells was negatively related with ERBB3 mRNA(r=-0.875，P<0.05). ［Conclusion］ The study shows that up-regulation of miR-152 could inhibit the proliferation，migration and invasion of UM-UC-3 cells by inhibition of ERBB3/Akt/c-myc and ERBB3/Akt/Snail signaling pathways. |
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