Glioblastoma is the most common and malignant form of primary central nervous tumor in adults. Long noncoding RNAs (lncRNAs) have been reported to play a pivotal role in modulating gene expression and regulating human tumor's malignant behaviors. In this study, we confirmed that lncRNA brain-derived neurotrophic factor antisense (BDNF-AS) was downregulated in glioblastoma tissues and cells, interacted and stabilized by polyadenylate-binding protein cytoplasmic 1 (PABPC1). Overexpression of BDNF-AS inhibited the proliferation, migration, and invasion, as well as induced the apoptosis of glioblastoma cells. In the in vivo study, PABPC1 overexpression combined with BDNF-AS overexpression produced the smallest tumo... More
Glioblastoma is the most common and malignant form of primary central nervous tumor in adults. Long noncoding RNAs (lncRNAs) have been reported to play a pivotal role in modulating gene expression and regulating human tumor's malignant behaviors. In this study, we confirmed that lncRNA brain-derived neurotrophic factor antisense (BDNF-AS) was downregulated in glioblastoma tissues and cells, interacted and stabilized by polyadenylate-binding protein cytoplasmic 1 (PABPC1). Overexpression of BDNF-AS inhibited the proliferation, migration, and invasion, as well as induced the apoptosis of glioblastoma cells. In the in vivo study, PABPC1 overexpression combined with BDNF-AS overexpression produced the smallest tumor and the longest survival. Moreover, BDNF-AS could elicit retina and anterior neural fold homeobox 2 (RAX2) mRNA decay through STAU1-mediated decay (SMD), and thereby regulated the malignant behaviors glioblastoma cells. Knockdown of RAX2 produced tumor-suppressive function in glioblastoma cells and increased the expression of discs large homolog 5 (DLG5), leading to the activation of the Hippo pathway. In general, this study elucidated that the PABPC1-BDNF-AS-RAX2-DLG5 mechanism may contribute to the anticancer potential of glioma cells and may provide potential therapeutic targets for human glioma.
