Long non-coding RNA HOXA-AS3 promotes glioma progression via miR-542-5p/HOXA1 axis

Abstract

Abstract Aims: Gliomas is one of the brain cancers belongs to the central nervous system(CNS) tumor. We previously showed that administration of natural product pristimerin significantly impaired the U373 cell progression by disturbing the miR-542-5p expression. But the upstream genes of miR-542-5p in glioma is still ill-defined. Methods: We used the RNA 22 v2 to predict the binding sites for lncRNAs and miRNAs. TCGA database was used to analyze the expression of HOXA-AS3, HOXA1 and WNT5A in glioma tissues. Survival curve of HOXA-AS3 in LGG patients was plotted. Glioma cell U373 and U251 were used to transfect with the siRNA to access the apoptosis rate and migration of cells. And tumor model was constructed to access the function of the HOXA-AS3 in vivo. Results: Our results showed the increased HOXA-AS3 and HOXA1 expression in glioma tissues. Cell growth/migration could be effectively suppressed by silencing HOXA-AS3or/and hsa-miR-542-5p in U373 cell, while cell apoptosis rate enhanced, which could be reserved by amplifying hsa-miR-542-5p expression. In addition, we found the decreased HOXA1 and WNT5A expression in HOXA-AS3silenced condition. In vivo experiments showed that silencing HOXA-AS3and hsa-miR-542-5p suppressed U373 tumor growth by inhibiting arginase-1 expression in tumor-associated macrophages. High level of HOXA-AS3, HOXA1, and WNT5A in tumor cell were associated with poor overall survival in patients with low-grade glioma, higher expression of which in tumor-infiltrating lymphocytes also correlated with worse patients’ outcome. Conclusions: Our results showed that HOXA-AS3 might promote glioma progression via regulating hsa-miR-542-5p/HOXA1and WNT5A.