LncRNA HOXD-AS1 promotes melanoma cell proliferation and invasion by suppressing RUNX3 expression

Am J Cancer Res. 2017 Dec 1;7(12):2526-2535. eCollection 2017.

Abstract

Long non-coding RNAs (lncRNAs) act as critical regulators of many malignant tumors cellular processes including cell proliferation, differentiation, apoptosis, invasion and metastasis. However, the functions and molecular mechanisms of lncRNA HOXD-AS1 in melanoma remain little known. In the present study, we observed that lncRNA HOXD-AS1 expression was remarkably higher in melanoma tissues compared to skin tissues with melanocytic nevus. Increased expression of lncRNA HOXD-AS1 correlated with poor survival of melanoma patients. Furthermore, functional experiments demonstrated that upregulated lncRNA HOXD-AS1 expression dramatically promoted cell proliferation and invasion of melanoma, while downregulation of lncRNA HOXD-AS1 showed a tumor inhibiting effects on melanoma cells in vitro. In vivo, data results showed that lncRNA HOXD-AS1 knockdown notably reduced tumor growth. Additionally, RNA immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP) assays revealed that lncRNA HOXD-AS1 could epigenetically suppress the expression of RUNX3 via binding to EZH2. Downregulation of RUNX3 attenuated the proliferation and invasion-inhibiting effects induced by lncRNA HOXD-AS1 knockdown in melanoma cells. Therefore, these results indicated that HOXD-AS1 may serve as a potential therapeutic target of melanoma.

Keywords: EZH2; HOXD-AS1; Melanoma; RUNX3; long non-coding RNA.