Triple-negative breast cancer (TNBC) is one of the malignant type of breast cancer. Previous study indicated that long noncoding RNA (lncRNA) ZEB1-AS1 was associated with the progression of several cancers. However, its underlying molecular mechanism in TNBC remains to be elucidated. In this study, ZEB1-AS1 expression was boosted in TNBC tissues and cell lines according to reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Inhibition of ZEB1-AS1 suppressed cell proliferation, migration, invasion, and promoted cell apoptosis in TNBC. Moreover, ZEB1-AS1 positively regulated ZEB1 expression. RT-qPCR disclosed ZEB1 expression was elevated in TNBC tissues and ZEB1 silence blocked TNBC progression. RNA pull-down and RNA immunoprecipitation assays revealed ZEB1-AS1 and ZEB1 both could bind with ELAVL1. ZEB1-AS1 maintained ZEB1 messenger RNA (mRNA) stability by binding with ELAVL1. In addition chromatin, immunoprecipitation and luciferase reporter assays confirmed that ZEB1 could bind with ZEB1-AS1 promoter and promoted ZEB1-AS1 expression. Rescue assays manifested ZEB1 overexpression could abolish the inhibitory effect caused by ZEB1-AS1 inhibition on TNBC progression. To sum up, ZEB1 induced-upregulation of ZEB1-AS1 maintained the stability of ZEB1 mRNA by binding with ELAVL1, which formed a feedback loop to facilitate TNBC progression. These findings might provide a new target for TNBC treatment.
Keywords: ELAVL1; ZEB1; ZEB1-AS1; triple negative breast cancer.
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