Knockdown of lncRNA ZNRD1‐AS1 inhibits progression of bladder cancer by regulating miR‐194 and ZEB1

BACKGROUND: Bladder cancer (BC) is a common urinary neoplasm with high incidence worldwide. Long noncoding RNA zinc ribbon domain containing 1 antisense RNA 1 (ZNRD1‐AS1) has been reported to be upregulated in BC. However, the exact role of ZNRD1‐AS1 as well as its mechanism remains poorly understood. METHODS: Zinc ribbon domain containing 1 antisense RNA 1, and its potential downstream genes microRNA‐194 (miR‐194) and zinc finger E‐box binding homeobox 1 (ZEB1) levels were detected via quantitative real‐time polymerase chain reaction or western blot. Cell proliferation, migration, invasion, and epithelial‐mesenchymal transition (EMT) were detected to assess the influences of ZNRD1‐AS1, miR‐194 and ZEB1 on BC cells by colony formation, cell counting kit‐8 (CCK‐8), transwell analysis or western blot. The relationship between miR‐194 and ZNRD1‐AS1 or ZEB1 was analyzed by luciferase activity analysis. The xenograft experiment was performed to assess the function of ZNRD1‐AS1 in vivo. RESULTS: Zinc ribbon domain containing 1 antisense RNA 1level was upregulated in BC. ZNRD1‐AS1 silence repressed proliferation, migration, invasion and EMT in BC cells. MiR‐194 was identified as a target of ZNRD1‐AS1, and miR‐194 upregulation repressed proliferation, migration, invasion, and EMT by ZNRD1‐AS1 sponging. ZEB1 was targeted via miR‐194 and its interference impeded proliferation, migration, invasion, and EMT. Moreover, ZNRD1‐AS1 regulated ZEB1 expression via miR‐194. Besides, inhibition of ZNRD1‐AS1 attenuated tumor growth by miR‐194/ZEB1 axis in vivo. CONCLUSION: Knockdown of ZNRD1‐AS1 suppressed BC cell development in vitro and in vivo via targeting miR‐194 to regulate ZEB1, indicating a novel avenue for treatment of BC.