Long non-coding RNA ZEB1-AS1 regulates miR-200b/FSCN1 signaling and enhances migration and invasion induced by TGF-β1 in bladder cancer cells

Abstract

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.

TGF-β and microRNA Interplay in Genitourinary Cancers

“…As a result, the expression of the miR-200b target, fascin1, is induced in bladder cancer cells, leading to activated migration and invasion. Induced ZEB1-AS1 expression inhibits apoptosis, promotes the cell cycle, and activates proliferation, as well as stimulates the growth of bladder cancer xenografts in mice [296]. According to another study, miR-200b targets and inhibits the expression of MMP16.…”

LncRNA ZEB1‐AS1 down‐regulation suppresses the proliferation and invasion by inhibiting ZEB1 expression in oesophageal squamous cell carcinoma

“…Our recent work identified many differential lncRNA through TCGA database, and we revealed that ZEB1‐AS1 was significantly up‐regulated in ESCA, but its precise functions remain unknown. It is a fact that ZEB1‐AS1 is closely correlated with tumour occurrence and development, such as bladder cancer, glioma, melanoma and non–small‐cell lung cancer, and these data suggest that ZEB1‐AS1 is involved in tumour progression via multiple different molecular mechanisms, suggesting the complexity of ZEB1‐AS1 function in these tumours. However, how ZEB1‐AS1 is regulated during ESCC development is still unclear, and therefore, herein, the expression pattern of ZEB1‐AS1 and its regulatory role in the proliferation and invasion ability of ESCC were investigated, which will propose ZEB1‐AS1/ZEB1 regulatory axis as an underlying therapeutic target for ESCC therapy.…”

LINC00961 inhibits the migration and invasion of colon cancer cells by sponging miR‐223‐3p and targeting SOX11

“…LncRNA FBXL19‐AS1 strengthens the breast cancer cells invasion and growth abilities by sponging miR‐718 . LncRNA ZEB1‐AS1 promotes TGF‐β1‐induced invasion of bladder tumor cells via targeting the miR‐200b/FSCN1 pathway . LINC00152 suppresses the development of esophageal carcinoma via sponging miR‐153‐3p and targeting FYN …”

“…15 LncRNA ZEB1-AS1 promotes TGF-β1-induced invasion of bladder tumor cells via targeting the miR-200b/FSCN1 pathway. 16 LINC00152 suppresses the development of esophageal carcinoma via sponging miR-153-3p and targeting FYN. 17 In this research, LINC00961 was downregulated in colon cancer.…”