The prognosis for patients with metastatic bladder cancer (BCa) is poor, and has not been improved by current treatment methods. Long noncoding RNAs (lncRNAs) are involved in the pathology of various tumors, including bladder cancer. However, the role of zinc finger E-box-binding homeobox 1-antisense 1 (ZEB1-AS1) in BCa progression and metastasis remains unclear. The present study determined the expression level of ZEB1-AS1 in BCa and additionally investigated the functional role of ZEB1-AS1 in BCa metastasis. Reverse transcription quantitative polymerase chain reaction analysis showed that ZEB1-AS1 was upregulated in BCa cells compared with normal epithelial cells. Functionally, knockdown of ZEB1-AS1 suppressed BCa cell migration and invasion in vitro , and metastasis in vivo . Mechanistic investigations revealed that ZEB1-AS1 bound to heterogenous nuclear ribonucleoprotein D0 (AUF1), thereby activating the translation of ZEB1 mRNA without affecting its mRNA level. In addition, ZEB1-AS1 was significantly upregulated in BCa tissues and muscle-invasive BCa cases. ROC curve analysis demonstrated that ZEB1-AS1 expression was associated with metastasis in patients with BCa. In conclusion, the data from the present study demonstrated that ZEB1-AS1 induced BCa metastasis via an AUF1-mediated translation activation of ZEB1 mRNA mechanism. ZEB1-AS1 may serve as a promising target for clinical intervention in advanced BCa.

IntroductionHigher expression levels of serine/threonine-protein kinase 1 (PLK1) are significantly associated with tumorigenesis and poor clinical prognoses. Consequently, PLK1 is considered a latent target in cancer treatment. We aimed to determine the cytotoxic effects of RO3280 on prostate cancer cells.Material and methodsPLK1 expression was investigated using real-time PCR and western blotting in prostate cancer tissues and paired normal tissues. Real-time cell analysis, cell counting kit-8 assays, and 5-ethynyl-2¢-deoxyuridine cell proliferation assays were applied for the examination of cell proliferation ability. Wound healing assays and transwell assays were used to assess the migratory and invasive abilities of the prostate cancer cell lines with or without RO3280 treatment. Moreover, the target genes and pathways were detected by transcriptomics RNA sequencing in the cells cultured in RO3280 and through a series of bioinformatics analyses. Finally, the Wnt/β-catenin pathway was screened out and verified by western blotting.ResultsWe observed the mRNA and protein overexpression of PLK1 in the prostate cancer cells and tissues. The inhibition of PLK1 by RO3280 significantly reduced the migratory, invasive, and proliferative properties of the RO3280-treated cancer cell lines compared with their controls. RO3280 mediated the inactivation of the Wnt/β-catenin pathway, and reduced the rates of cell proliferation, migration, and invasion in prostate cancer cells.ConclusionsThis study’s findings are significant owing to the identification of the specific anticancer mechanism of RO3280, which may have therapeutic effects. This trial provides clarity on the feasibility of the use of RO3280 as a cancer therapeutic agent for prostate cancer.