Downregulation of lncRNA-HOXA11-AS modulates proliferation and stemness in Glioma cells

Background: Glioma stem cells (GSCs) represent a subpopulation of cells within glioma that are characterized by chemotherapy resistance and tumor recurrence. GSCs are therefore important therapeutic target for glioma therapy. Long non-coding RNAs (lncRNAs) have been shown to regulate important functions in cancer. HOXA11-AS is one such lncRNA and has been shown to regulate cell proliferation via promotion of cell cycle progression in glioblastoma (GBM) cells. However, the specific roles of HOXA11-AS in GSCs remain unclear. Methods: Here we investigated the role of HOXA11-AS in driving GSC stemness properties via sphere-forming and protein chip assays. Results: Gain-of-function as well as loss-of-function results showed that the HOXA11-AS maybe a critical modulator in GBM recurrence as demonstrated by cell sphere-forming ability. Furthermore, we showed that induced expression of HOXA11-AS does increase the levels of stemness-related transcription factors (Oct4/Sox17/Sox2) in U87MG cells. In vivo xenograft experiments using the HOXA11-AS knockdown U87MG cells revealed that downregulation of HOXA11-AS could strongly inhibit tumor growth. Furthermore, we found that HOXA11-AS knockdown decreased the expression of cancer stemness markers in vivo. Conclusions: Collectively, these data suggests that HOXA11-AS is involved in GSC stemness and supports its clinical significance as a important therapeutic target in glioma.