Abstract
BackgroundEmerging studies show that long noncoding RNAs (lncRNAs) play important roles in carcinogenesis and cancer progression. The lncRNA ZEB1 antisense 1 (ZEB1-AS1) derives from the promoter region of ZEB1 and we still know little about its expressions, roles and mechanisms.MethodsRACE was used to obtain the sequence of ZEB1-AS1. RNA interference was used to decrease ZEB1-AS1 expression. Adenovirus expression vector was used to increase ZEB1-AS1 expression. CHIP and RIP were used to detect the epigenetic mechanisms by which ZEB1-AS1 regulated ZEB1. CCK8 assay, wound healing assay and transwell assay were used to measure proliferation and migration of prostate cancer cells.ResultsIn this study, in prostate cancer cells, we found that RNAi-mediated downregulation of ZEB1-AS1 induced significant ZEB1 inhibition while artificial overexpression of ZEB1-AS1 rescued ZEB1 expression, which means that ZEB1-AS1 promotes ZEB1 expression. Also, ZEB1-AS1 indirectly inhibited miR200c, the well-known target of ZEB1, and upregulated miR200c’s target BMI1. Mechanistically, ZEB1-AS1 bound and recruited histone methyltransferase MLL1 to the promoter region of ZEB1, induced H3K4me3 modification therein, and activated ZEB1 transcription. Biologically, ZEB1-AS1 promoted proliferation and migration of prostate cancer cells.ConclusionsCollectively, ZEB1-AS1 functions as an oncogene in prostate cancer via epigenetically activating ZEB1 and indirectly regulating downstream molecules of ZEB1.
Highlights
Emerging studies show that long noncoding RNAs play important roles in carcinogenesis and cancer progression
Because BMI1 is directly repressed by miR200c [13], the transcription of which is directly inhibited by Zinc finger E-box-binding protein 1 (ZEB1), we speculated that the ZEB1-miR200c-BMI regulation pathway may play an
A series of primers were used in PCR amplification to identify ZEB1-AS1, which derived from the promoter region of ZEB1 gene (−110 ~ −2646 bp)
Summary
Emerging studies show that long noncoding RNAs (lncRNAs) play important roles in carcinogenesis and cancer progression. The lncRNA ZEB1 antisense 1 (ZEB1-AS1) derives from the promoter region of ZEB1 and we still know little about its expressions, roles and mechanisms. The zinc finger E-box-binding protein 1 (ZEB1, known as ZFHX1A, AREB6, or ΔEF1) is a transcriptional factor that plays important roles in physiology and tumorigenesis. Su et al Molecular Cancer (2017) 16:142 important role in prostate cancer development and progression. Xist, a lncRNA derived from the inactive X, plays an essential role in X inactivation in mammals, and is itself controlled by a complex interplay of other lncRNAs such as Tsix, which is transcribed from the antisense strand of Xist [14, 15]
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