Background
The effect of competing endogenous RNA (ceRNA) can regulate gene expression by competitively binding microRNAs. Fascin-1 (FSCN1) plays an important role in the regulation of cellular migration and invasion during tumor progression, but how its regulatory mechanism works through the ceRNA effect is still unclear in bladder cancer (BLCA).
Methods
The role of fascin-1,
miR-200b
, and
ZEB1-AS1
in BLCA was investigated in vitro and in vivo. The interaction between fascin-1,
miR-200b
, and
ZEB1-AS1
was identified using bioinformatics analysis, luciferase activity assays, RNA-binding protein immunoprecipitation (RIP), quantitative PCR, and western blotting. Loss (or gain)-of-function experiments were performed to investigate the biological roles of
miR-200b
and
ZEB1-AS1
on migration, invasion, proliferation, cell apoptosis, and cell cycle.
Results
ZEB1-AS1
functions as a competing endogenous RNA in BLCA to regulate the expression of fascin-1 through
miR-200b
. Moreover, the oncogenic long non-coding RNA
ZEB1-AS1
was highly expressed in BLCA and positively correlated with high tumor grade, high TNM stage, and reduced survival of patients with BLCA. Moreover,
ZEB1-AS1
downregulated the expression of
miR-200b
, promoted migration, invasion, and proliferation, and inhibited apoptosis in BLCA. Furthermore, we found TGF-β1 induced migration and invasion in BLCA by regulating the
ZEB1-AS1
/
miR-200b
/FSCN1 axis.
Conclusion
The observations in this study identify an important regulatory mechanism of fascin-1 in BLCA, and the TGF-β1/
ZEB1-AS1
/
miR-200b
/FSCN1 axis may serve as a potential target for cancer therapeutic purposes.
Electronic supplementary material
The online version of this article (10.1186/s13046-019-1102-6) contains supplementary material, which is available to authorized users.