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

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.

Long Non-Coding RNA HOXA11-AS Modulates Proliferation, Apoptosis, Metastasis and EMT in Cutaneous Melanoma Cells Partly via miR-152-3p/ITGA9 Axis

“…27 The silence of HOXA11-AS was also showed to reduce proliferation and metastasis but expedite apoptosis of glioma cells. 28 Lu et al unraveled that HOXA11-AS knockdown reduced proliferation and invasion abilities, but induced apoptosis of uveal melanoma (UM) cells. 29 But the role of HOXA11-AS in cutaneous melanoma is almost unclear.…”

Research on HOXA11-AS in Malignant Tumors

“…Subsequently, on this basis, another study of the group reported that HOXA11-AS is highly expressed in non-small cell lung cancer tissues and cell lines. The proliferation, migration, invasion, and invasion of non-small cell lung cancer cells after HOXAl1-AS knockout Both tumorigenicity and angiogenesis are inhibited, while apoptosis is increased, and the cell cycle is arrested in GO/G1 or G2/M phase [21]. Further research found that HOXA11-AS may exert its above biological functions in non-small cell lung cancer by regulating the expression of miR-642b-3p and PDE4D [22].…”

Long Non-Coding RNAs in Diagnosis, Treatment, Prognosis, and Progression of Glioma: A State-of-the-Art Review

“…Overall, almost all oncogene lncRNAs regulate the cell cycle, promote tumor proliferation, inhibit apoptosis, and induce tumor invasiveness and migration. While lncRNAs such as XIST (162-172), CRDNE (173-179), FOXD2-AS1 (186)(187)(188)(189)(190)(191)(192)(193)(194), ANRIL (195)(196)(197), HOXA11-AS (198)(199)(200)(201)(202)(203), TP73-AS1 (204)(205)(206), and DANCR (207-210) are only known as tumor inducers, the ultimate function of some lncRNAs is controversial. For instance, for MALAT1, NEAT1, and TUG1, both oncogenic and tumor suppressor effects have been reported.…”