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  • 蒋 逊,肖天卫,鲁贺磊,等.微小RNA-506-3p调控UHRF1抑制大肠癌细胞转移的机制[J].同济大学学报(医学版),2019,30(3):298-304.    [点击复制]
  • JIANG Xun,XIAO Tian-wei,LU He-lei,et al.MiR-506-3p suppresses metastasis of colorectal cancer by targeting UHRF1[J].同济大学学报(医学版),2019,30(3):298-304.   [点击复制]
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微小RNA-506-3p调控UHRF1抑制大肠癌细胞转移的机制
蒋逊,肖天卫,鲁贺磊,刘忠臣,王峰
0
(同济大学附属第十人民医院胃肠外科,上海 200072;云南省临沧市双江县人民医院普外科,云南 临沧 677300)
摘要:
目的 探讨微小RNA-506-3p(miR-506-3p)通过调控含PHD及指环结构域的类泛素蛋白1(UHRF1)的表达,进而影响大肠癌细胞转移能力的机制。方法 利用生物信息学的方法预测并筛选UHRF1上游可能发挥调控作用的miRNA-506-3p;在大肠癌细胞及组织中分别检测miR-506-3p及UHRF1的表达水平并分析其相关性;运用荧光素酶报告基因技术检测miR-506-3p与UHRF1 3′非翻译区(3′UTR)特异性结合的情况;荧光定量PCR(qRT-PCR)及Western blot检测大肠癌细胞转染miR-506-3p类似物(mimics)后对UHRF1表达水平的影响;构建UHRF1过表达的大肠癌稳转细胞株,分别转染miR-506-3p mimics及其对照序列(mimics control)后,利用Transwell实验检测处理前后大肠癌细胞转移能力的变化。结果 相对于正常大肠上皮细胞及癌旁组织而言,miR-506-3p在大肠癌细胞及组织中的表达均下调(均P<0.05),且与UHRF1的表达水平呈负相关(r=-0.456,P=0.044);miR-506-3p通过其“种子序列”与UHRF1 3′UTR特异性结合(P<0.01),并减少了UHRF1的mRNA及蛋白表达(均P<0.01);转染miR-506-3p mimics抑制了大肠癌LoVo细胞的转移能力(P<0.01),而在此基础上增加UHRF1的表达则逆转了miR-506-3p的抑制作用(P<0.01)。结论 miR-506-3p通过调控UHRF1抑制了大肠癌细胞的转移能力,在大肠癌中发挥抑癌基因的作用。
关键词:  大肠癌  转移  microRNA-506-3p  含PHD及指环结构域的类泛素蛋白1
DOI:10.16118/j.1008-0392.2019.03.007
投稿时间:2018-11-20
基金项目:国家自然科学基金(81301753)
MiR-506-3p suppresses metastasis of colorectal cancer by targeting UHRF1
JIANG Xun,XIAO Tian-wei,LU He-lei,LIU Zhong-chen,WANG Feng
(Dept. of General Surgery, Tenth People’s Hospital, Tongji University, Shanghai 200072, China;Dept. of General Surgery, Shuangjiang County People’s Hospital, Lincang 677300, Yunnan Province, China)
Abstract:
Objective To explore the effect of microRNA-506-3p(miR-506-3p) on metastasis of colorectal cancer (CRC) and its relation to UHRF1 (ubiquitin-like, containing PHD and ring finger domain 1). Methods Bioinformatics screening was performed to predict UHRF1 as a potential target of miR-506-3p. The expression of miR-506-3p and UHRF1 was detected by qRT-PCR in 20 pairs of CRC and adjacent non-tumoral tissue samples, CRC cell lines LoVo, SW480, HT29, Caco-2 and normal intestinal epithelial cell line NCM460. Luciferase reporter assays, qRT-PCR, Western blotting and Transwell assays were used to evaluate the effects of miR-506-3p on the regulation of UHRF1 in CRC cells. Results Bioinformatics analysis indicated that UHRF1 was a putative target of miR-506-3p. The expression of miR-506-3p decreased in CRC cell lines and in CRC tissues compared to adjacent non-cancerous tissues, and it was negatively correlated with UHRF1 expression. Luciferase reporter assay indicated that miR-506-3p directly bound to 3′-UTR of UHRF1. Over-expression of miR-506-3p decreased the expression of UHRF1. In vitro migration assay showed that synthetic miR-506-3p suppressed UHRF1 expression and reduced metastasis of CRC cells. Conclusion miR-506-3p suppresses metastasis of CRC through targeting UHRF1 and it may play an important role as a tumor suppressor in CRC.
Key words:  colorectal cancer  metastasis  microRNA-506-3p  ubiquitin-like containing PHD and ring finger domain 1

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