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

Bladder Cancer

Cancer Med. 2020 Aug 30. doi: 10.1002/cam4.3373. Online ahead of print.


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.