title: 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.
abstract: 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.
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Xue
authors.affiliation: Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Pang
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Huijin
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Pan
authors.affiliation: Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
mesh_terms: D000368:Aged; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000473:pathology*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D062085:RNA, Long Noncoding / Q000235:genetics*; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology*; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D002352:Carrier Proteins; C502658:FSCN1 protein, human; D018398:Homeodomain Proteins; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D062085:RNA, Long Noncoding; D012097:Repressor Proteins; D014157:Transcription Factors; C515159:UCA1 RNA, human; C486307:ZEB1 protein, human; C492363:ZEB2 protein, human; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1
keywords: Bladder cancer; Hsa-miR-145; UCA1; epithelial to mesenchymal transition; long non-coding RNA