Abstract
ABSTRACT HOTAIR, as one of the few well-studied oncogenic lncRNAs, is involved in human tumorigenesis and is dys-regulated in most human cancers. The transcription co-activator factor YAP1 is broadly expressed in many tissues, and promotes cancer metastasis and progression. However, the precise biological roles of HOTAIR and YAP1 in cancer cells remain unclear. In this study, we showed that HOTAIR regulates H3K27 histone modification in the promoter of miR-200a to mediate miR-200a expression by recruiting EZH2. YAP1, as a potential target gene of miR-200a, aggravated the effects of miR-200a on the migration and invasion of HeLa cells. YAP1 activated the transcription of RPL23, which is a novel downstream transcriptional-regulator of YAP1. Agreement with this, the expression of YAP1 and RPL23 was dramatically decreased after injecting HeLa cells transfected with siHOTAIR in a xenograft mouse model. Accordingly, we propose a novel model of the molecular mechanism by which HOTAIR promotes the migration and invasion of cancer cells involving the miR-200a-3p/YAP1/RPL23 axis.
Highlights
HOTAIR, as one of the few well-studied oncogenic lncRNAs, is involved in human tumorigenesis and is dysregulated in most human cancers
As a target gene of miR-200a-3p,YAP1 promotes the migration and invasion of HeLa cells by mediating the downstream transcription of RPL23 which normally functions as a cancer-promoting factor
We propose a novel model of the molecular mechanism by which HOTAIR promotes the migration and invasion of cancer cells involving the miR-200a-3p/YAP1/RPL23 axis
Summary
The expression levels of HOTAIR and YAP1 were measured by quantitative PCR (qPCR), immunoblotting. Wound-healing and transwell assays were used to examine the invasive abilities of HeLa cells. Luciferase reporter assays and CHIP were used to determine how YAP1 regulates RPL23. A xenograft mouse mode was used to assess the correlation between HOTAIR and YAP1 in vivo. A total of 40 nM siRNA targeted against HOTAIR (siHOTAIR-I or siHOTAIR-II) or negative control siRNA (siNC) were transfected into HeLa cells using RNAi-mate. HOTAIR expression levels were measured 48 h after transfection by qPCR (see below). HeLa cells were transfected with 40nM of siRNA targeted against YAP1 or RPL23 to silence gene expression. Cells were harvested 48 h after transfection, and protein expression was assessed by western blotting (see below)
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