Long noncoding RNA homeobox (HOX) A11-AS promotes malignant progression of glioma by targeting miR-124-3p

Yang Sun, Ji-Xue Yang, Bei Liu,  Bao-Ying Yang,  Qiang Meng

Abstract:

Glioma is the most common and serious form of primary tumor in adult central nervous system. HOXA11-AS is a LncRNA located in the HOXA gene cluster. In the present study, we investigated the expression and function of LncRNA HOXA11-AS in glioma tissues and cells. We found that LncRNA HOXA11-AS expression was markedly elevated in glioma tissues compared to normal brain tissues. The LncRNA HOXA11-AS expression in cases of high-grade glioma was significantly higher than that in cases of low-grade. Patients with high LncRNA HOXA11-AS expression had shorter OS time than those with low LncRNA HOXA11-AS expression. Moreover, silencing LncRNA HOXA11-AS inhibited cell proliferation, increased apoptosis, and inhibited invasion and migration of glioma cells. Overexpression of LncRNA HOXA11-AS increased cell proliferation, decreased apoptosis, and increased invasion and migration of glioma cells. miR-124-3p has relevant binding sites in HOXA11-AS. Silencing HOXA11-AS significantly increased miR-124-3p expression. The miR-124-3p overexpression decreased the luciferase activity of the pMIR luciferase reporter containing HOXA11-AS-WT but not HOXA11-AS-MUT. Moreover, miR-124-3p was pulled down by HOXA11-AS probe. miR-124-3p mimics inhibited cell proliferation, increased apoptosis, and inhibited invasion and migration of glioma cells. miR-124-3p mimics significantly suppressed overexpression of HOXA11-AS-induced increase of proliferation, decrease of apoptosis and increase of invasion and migration. miR-124-3p inhibitors suppressed the effect of siHOXA11-AS on proliferation, apoptosis, invasion and migration. In summary, the findings highlight the importance of LncRNA HOXA11-AS/miR-124-3p axis in the regulation of glioma progression. LncRNA HOXA11-AS/miR-124-3p might serve as a potential therapeutic target in glioma treatment in the future.