miR-145 and miR-133a function as tumour suppressors and directly regulate FSCN1 expression in bladder cancer.
miR-145 and miR-133a function as tumour suppressors and directly regulate FSCN1 expression in bladder cancer.
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DOI：
10.1038/sj.bjc.6605570
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发表时间：
2010-03-02
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
我们最近在膀胱癌（BC）中发现了包括miR - 145和miR - 133a在内的下调微小RNA。本研究的目的是确定miR - 145所靶向的基因，miR - 145是膀胱癌中下调最显著的微小RNA。
我们从miR - 145转染细胞的基因表达谱中关注到肌动蛋白集束蛋白同源物1（FSCN1）。利用荧光素酶报告基因实验来确定FSCN1 mRNA的实际结合位点。通过细胞生长、划痕愈合和基质胶侵袭实验评估细胞活力。对膀胱癌标本进行FSCN1的免疫组织化学和miR - 145的原位杂交。
通过数据库搜索，miR - 133a以及miR - 145都具有FSCN1 mRNA的靶序列，并且这两种微小RNA都抑制了FSCN1的mRNA和蛋白质表达。荧光素酶报告基因实验显示miR - 145和miR - 133a直接与FSCN1 mRNA结合。在miR - 145、miR - 133a和si - FSCN1转染细胞中，细胞活力受到显著抑制。原位杂交显示在FSCN1强染色的肿瘤病变中miR - 145表达明显受到抑制。浸润性膀胱癌（n = 46）中FSCN1的免疫组化评分显著高于非浸润性膀胱癌（n = 20）（P = 0.0055）。
肿瘤抑制性的miR - 145和miR - 133a在膀胱癌中直接调控致癌的FSCN1。
We have recently identified down-regulated microRNAs including miR-145 and miR-133a in bladder cancer (BC). The aim of this study is to determine the genes targeted by miR-145, which is the most down-regulated microRNA in BC. We focused on fascin homologue 1 (FSCN1) from the gene expression profile in miR-145 transfectant. The luciferase assay was used to confirm the actual binding sites of FSCN1 mRNA. Cell viability was evaluated by cell growth, wound-healing, and matrigel invasion assays. BC specimens were subjected to immunohistochemistry of FSCN1 and in situ hybridisation of miR-145. The miR-133a as well as miR-145 had the target sequence of FSCN1 mRNA by the database search, and both microRNAs repressed the mRNA and protein expression of FSCN1. The luciferase assay revealed that miR-145 and miR-133a were directly bound to FSCN1 mRNA. Cell viability was significantly inhibited in miR-145, miR-133a, and si-FSCN1 transfectants. In situ hybridisation revealed that miR-145 expression was markedly repressed in the tumour lesion in which FSCN1 was strongly stained. The immunohistochemical score of FSCN1 in invasive BC (n=46) was significantly higher than in non-invasive BC (n=20) (P=0.0055). Tumour suppressive miR-145 and miR-133a directly control oncogenic FSCN1 in BC.
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影响因子：
56.9
作者：
Lagos-Quintana, M;Rauhut, R;Tuschl, T
通讯作者：
Tuschl, T
DOI：
10.1073/pnas.0808042106
发表时间：
2009-03-03
影响因子：
11.1
作者：
Sachdeva, Mohit;Zhu, Shoumin;Mo, Yin-Yuan
通讯作者：
Mo, Yin-Yuan
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
影响因子：
3.3
作者：
McCarthy, John J.;Esser, Karyn A.
通讯作者：
Esser, Karyn A.
影响因子：
6.4
作者：
Qiu, Dongmei;Katanoda, Kota;Sobue, Tomotaka
通讯作者：
Sobue, Tomotaka