Long non-coding RNA urothelial cancer-associated 1 promotes bladder cancer cell migration and invasion by way of the hsa-miR-145-ZEB1/2-FSCN1 pathway.
Long non-coding RNA urothelial cancer-associated 1 promotes bladder cancer cell migration and invasion by way of the hsa-miR-145-ZEB1/2-FSCN1 pathway.
复制标题
长链非编码RNA尿路上皮癌相关1通过hsa-miR-145-ZEB1/2-FSCN1通路促进膀胱癌细胞迁移和侵袭
DOI：
10.1111/cas.12844
复制
发表时间：
2016-01
期刊：
影响因子：
5.7
通讯作者：
Chen W
中科院分区：
文献类型：
--
作者：
Xue M;Pang H;Li X;Li H;Pan J;Chen W
许多研究表明，几种长链非编码RNA（lncRNA）在膀胱癌的发生和发展中起着关键作用。尿路上皮癌相关长链非编码RNA 1（lncRNA-UCA 1）在膀胱癌组织和细胞中高度表达，已被证明在调节膀胱癌细胞侵袭性表型中起重要作用。然而，关于lncRNA-UCA 1介导的膀胱癌细胞迁移和侵袭的分子机制知之甚少。在这里，我们表明lncRNA-UCA 1的过表达可以诱导EMT并增加膀胱癌细胞的迁移和侵袭能力。从机制上讲，lncRNA-UCA 1通过上调锌指E盒结合同源框1和2（ZEB 1和ZEB 2）的表达水平诱导膀胱癌细胞的EMT，并通过肿瘤抑制性hsa-miR-145及其靶基因肌动蛋白结合蛋白fascin homologue 1（FSCN 1）调节膀胱癌细胞的迁移和侵袭。此外，我们还观察到膀胱癌标本中lncRNA-UCA 1和ZEB 1/2表达之间呈正相关，lncRNA-UCA 1和hsa-miR-145表达之间呈负相关。重要的是，我们发现lncRNA-UCA 1抑制hsa-miR-145的表达以上调ZEB 1/2，而抑制hsa-miR-145可以上调膀胱癌细胞中lncRNA-UCA 1的表达。此外，lncRNA-UCA 1外显子2和3内的hsa-miR-145结合位点有助于lncRNA-UCA 1和hsa-miR-145的相互负调控。综上所述，我们的结果确定lncRNA-UCA 1部分通过hsa-miR-145/ZEB 1/2/FSCN 1途径增强膀胱癌细胞的迁移和侵袭。因此，lncRNA-UCA 1可能成为膀胱癌侵袭和转移的一个有希望的治疗靶点。
Numerous studies suggest that several long non‐coding RNAs (lncRNAs) play critical roles in bladder cancer development and progression. Long non‐coding RNA urothelial cancer‐associated 1 (lncRNA‐UCA1) is highly expressed in bladder cancer tissues and cells, and it has been shown to play an important role in regulating aggressive phenotypes of bladder cancer cells. However, little is known about the molecular mechanism of lncRNA‐UCA1‐mediated bladder cancer cell migration and invasion. Here, we show that overexpression of lncRNA‐UCA1 could induce EMT and increase the migratory and invasive abilities of bladder cancer cells. Mechanistically, lncRNA‐UCA1 induced EMT of bladder cancer cells by upregulating the expression levels of zinc finger E‐box binding homeobox 1 and 2 (ZEB1 and ZEB2), and regulated bladder cancer cell migration and invasion by tumor suppressive hsa‐miR‐145 and its target gene the actin‐binding protein fascin homologue 1 (FSCN1). Furthermore, we also observed a positive correlation between lncRNA‐UCA1 and ZEB1/2 expression, and a negative correlation between lncRNA‐UCA1 and hsa‐miR‐145 expression in bladder cancer specimens. Importantly, we found that lncRNA‐UCA1 repressed hsa‐miR‐145 expression to upregulate ZEB1/2, whereas the suppression of hsa‐miR‐145 could upregulate lncRNA‐UCA1 expression in bladder cancer cells. Moreover, the binding site for hsa‐miR‐145 within exons 2 and 3 of lncRNA‐UCA1 contributed to the reciprocal negative regulation of lncRNA‐UCA1 and hsa‐miR‐145. Taken together, our results identified that lncRNA‐UCA1 enhances bladder cancer cell migration and invasion in part through the hsa‐miR‐145/ZEB1/2/FSCN1 pathway. Therefore, lncRNA‐UCA1 might act as a promising therapeutic target for the invasion and metastasis of bladder cancer.