Targeting HOXA11‐AS to mitigate prostate cancer via the glycolytic metabolism: In vitro and in vivo

Abstract

AbstractAs oncogenes or oncogene suppressors, long‐stranded non‐coding RNAs are essential for the formation and progression of human tumours. However, the mechanisms behind the regulatory role of RNA HOXA11‐AS in prostate cancer (PCa) are unclear. PCa is a common malignant tumour worldwide, and an increasing number of studies have focused on its metabolic profile. Studies have shown that the long non‐coding RNA (lncRNA) HOXA11‐AS is aberrantly expressed in many tumours. However, the role of HOXA11‐AS in PCa is unclear. This work aimed to determine how HOXA11‐AS regulated PCa in vitro and in vivo. We first explored the clinical role of HOXA11‐AS in PCa using bioinformatics methods, including single sample gene set enrichment analysis (ssGSEA), weighted gene co‐expression network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO)‐logistics systematically. In this study, PCa cell lines were selected to assess the PCa regulatory role of HOXA11‐AS overexpression versus silencing in vitro, and tumour xenografts were performed in nude mice to assess tumour suppression by HOXA11‐AS silencing in vivo. HOXA11‐AS expression was significantly correlated with clinicopathological factors, epithelial‐mesenchymal transition (EMT) and glycolysis. Moreover, key genes downstream of HOXA11‐AS exhibited good clinical diagnostic properties for PCa. Furthermore, we studied both in vitro and in vivo effects of HOXA11‐AS expression on PCa. Overexpression of HOXA11‐AS increased PCa cell proliferation, migration and EMT, while silencing HOXA11‐AS had the opposite effect on PCa cells. In addition, multiple metabolites were downregulated by silencing HOXA11‐AS via the glycolytic pathway. HOXA11‐AS silencing significantly inhibited tumour development in vivo. In summary, silencing HOXA11‐AS can inhibit PCa by regulating glucose metabolism and may provide a future guidance for the treatment of PCa.