Novel insights into the mechanisms by which lncRNAHOTAIR regulates migration and invasion in HeLa cells

Abstract

Background HOTAIR, as one of the few well-studied oncogenic lncRNAs, is involved in human tumorigenesis and is dysregulated 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. Methods 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. Result In this study, we showed that HOTAIR regulates H3K27 histone modification in the promoter of miR-200a to mediate miR-200a expression byrecruiting 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 target of YAP1 transcriptional regulation. Agreement with this, the expression of YAP1 and RPL23 was dramatically decreased after injecting HeLa cells transfected with siHOTAIR in a xenograft mouse model. Conclusion These elucidates that HOTAIR, as an oncogenic lncRNA, recruits EZH2 to reduce miR-200a-3p expression via H3k27 trimethylation in the miR-200a-3p promoter. As a target gene of miR-200a-3p,YAP1 then promotes the migration and invasion of HeLa cells by mediating the downstream transcription of RPL23 which normally functions as a cancer-promoting factor. 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.