Long non-coding RNA (lncRNA) HOXD-AS2 promotes glioblastoma cell proliferation, migration and invasion by regulating the miR-3681-5p/MALT1 signaling pathway

Abstract

ABSTRACT Glioblastoma (GBM) is the most lethal type of brain cancer. An increasing number of studies suggest that long non-coding RNAs (lncRNAs) are implicated in tumor progression. LncRNA HOXD‐AS2 was reported to be highly expressed in glioma and associated with glioma grade and poor prognosis. However, the molecular mechanism remains to be elucidated. In this study, we first analyzed differentially expressed lncRNAs in glioblastoma using RNA-seq dataset (156 GBM samples and 5 adjacent normal samples in TCGA (Cancer Genome Atlas) and GTEx (Genotype-Tissue Expression) database). HOXD-AS2 was found to be significantly up-regulated in GBM tissues, which was further confirmed in GBM patient tumor samples and GBM cell lines. Silencing HOXD-AS2 inhibited cell proliferation, migration and invasion, and promoted cell apoptosis. We further identified and validated miR-3681-5p as a target of HOXD-AS2, and miR-3681-5p was negatively regulated by HOXD-AS2. By negatively affecting miR-3681-5p, HOXD-AS2 could promote the expression of MALT1 to augment the aggressiveness of GBM cells. miR-3681-5p overexpression or MALT1 knockdown attenuated aggressiveness of GBM cells. Importantly, silencing HOXD-AS2 suppressed tumorigenesis of GBM cells in the xenograft mouse model. Collectively, our study clarified the role of miR-3681-5p/MALT1 axis underlying the oncogenic function of lncRNA HOXD-AS2 in GBM. Future work is required to study the mechanism by which HOXD-AS2 is upregulated in GBM cells, which can provide novel insights into therapeutic intervention for GBM treatment.