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人源微小RNA-1在膀胱癌中下调长链非编码RNA尿路上皮癌相关因子1

Hsa-miR-1 downregulates long non-coding RNA urothelial cancer associated 1 in bladder cancer.

作者信息

Wang Tiantian, Yuan Jiancheng, Feng Nenggui, Li Yuchi, Lin Zheguang, Jiang Zhimao, Gui Yaoting

出版信息

Tumour Biol. 2014 Oct;35(10):10075-84. doi: 10.1007/s13277-014-2321-2.

Abstract

MicroRNAs (miRNAs) are known to mainly target protein-coding genes at post-transcriptional level, resulting in mRNA destabilization and/or translational repression. Long non-coding RNAs (lncRNAs) are emerging as a novel set of targets for miRNAs. Here, we report that downregulated hsa-miR-1 and upregulated lncRNA urothelial cancer associated 1 (UCA1) were inversely expressed in bladder cancer. Hsa-miR-1 decreased the expression of UCA1 in bladder cancer cells in an Ago2-slicer-dependent manner. The binding site between UCA1 and hsa-miR-1 was confirmed. Overexpression of hsa-miR-1 inhibited bladder cancer cell growth, induced apoptosis, and decreased cell motility. Knockdown of UCA1 expression phenocopied the effects of upregulation of hsa-miR-1. Transfection of UCA1 expression vector partly reversed the changes caused by transfection of pre-miR-1 plasmids. This study provides evidence for hsa-miR-1 to play tumor suppressive roles via downregulating lncRNA UCA1 in bladder cancer, which may have potential therapeutic significance.

摘要

已知微小RNA(miRNA)主要在转录后水平靶向蛋白质编码基因,导致信使核糖核酸(mRNA)不稳定和/或翻译抑制。长链非编码RNA(lncRNA)正成为miRNA的一组新靶点。在此,我们报告下调的人miR-1和上调的lncRNA尿路上皮癌相关1(UCA1)在膀胱癌中呈反向表达。人miR-1以AGO2切割依赖的方式降低膀胱癌细胞中UCA1的表达。证实了UCA1与人miR-1之间的结合位点。人miR-1的过表达抑制了膀胱癌细胞的生长,诱导了细胞凋亡,并降低了细胞运动性。敲低UCA1表达模拟了人miR-1上调的作用。转染UCA1表达载体部分逆转了转染前体miR-1质粒所引起的变化。本研究为hsa-miR-1在膀胱癌中通过下调lncRNA UCA1发挥肿瘤抑制作用提供了证据,这可能具有潜在的治疗意义。

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