MNX1-AS1 Enhances Cholangiocarcinoma Cell Proliferation and Migration by Increasing HuR-Mediated mRNA Stability of MNX1

Abstract

Introduction: Cholangiocarcinoma (CCA) accounts for 2% of all malignancies and it has shown an increased in recent years. Several studies have elucidated that long non-coding RNAs (lncRNAs) participate in processes associated with cancer development. LncRNA MNX1-AS1 (motor neuron and pancreas homeobox 1-antisense RNA1) has been identified as a malignant promoter in various cancers. Nevertheless, its biological role in CCA has not been explored yet. Thus, the aim of this study is to evaluate the underlying mechanism and functions of lncRNA MNX1-AS1 in CCA. Methods: By searching circlncRNAnet and The Cancer Genome Atlas (TCGA) database, we determined the expression of MNX1-AS1 and MNX1 (motor neuron and pancreas homeobox 1) in CCA tissue. Reverse-transcription and quantitative real-time PCR (RT-qPCR) detected gene expression. The underlying mechanism of MNX1-AS1 was assessed by luciferase reporter assay, ribonucleic acid (RNA) pull-down assay and RNA immunoprecipitation (RIP) assay. Results: MNX1-AS1 and MNX1 were overexpressed in CCA tissue and CCA cells. Their expression level was positively correlated to each other. Moreover, it was validated that MNX1-AS1 could positively regulate MNX1 messager ribonucleic acid (mRNA) expression and could bind to embryonic lethal, abnormal vision like RNA binding protein 1 (ELAVL1;Also known as HuR). Furthermore, HuR bound to MNX1 mRNA what promoted the mRNA stability of MNX1. Finally, rescue assays proved that the reduced CCA cell proliferation and migration induced by MNX1-AS1 deficiency could be reversed by MNX1 overexpression. Conclusions: Our work confirmed that MNX1-AS1 strengthened CCA cell malignant behaviors through HuR interaction what stabilized MNX1 expression.