Long noncoding RNA UCA1 promotes bladder cancer cell migration and invasion via hsa-miR-145/ ZEB1/2 /FSCN1 pathway

Numerous studies suggest that several long noncoding RNAs (lncRNAs) play critical roles in bladder cancer development and progression. LncRNA-urothelial cancer associated 1 (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 demonstrated that overexpression of lncRNA-UCA1 could induce epithelial to mesenchymal transition (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 of 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, while the suppression of hsa-miR-145 could upregulate lncRNA-UCA1 expression in bladder cancer cells. Moreover, the binding site for hsa-miR-145 within exon 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 though 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. This article is protected by copyright. All rights reserved.

Cancer science. 2015 Nov 06 [Epub ahead of print]

Mei Xue, Huan Pang, Xu Li, Huijin Li, Jingjing Pan, Wei Chen

Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China. , Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China. , Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China. , Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China. , Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China. , Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.

PubMed