Abstract
Differential expression of long noncoding RNAs (lncRNA) plays a key role in the development of gliomas. Because gliomas are the most common primary central nervous system tumor and glioblastomas have poor prognosis, it is urgent to develop new diagnostic methods. We have previously reported that lncRNA HOXD-AS2, which is specifically up-regulated in gliomas, can activate cell cycle and promote the development of gliomas. It is expected to be a new marker for molecular diagnosis of gliomas, but little is known about HOXD-AS2. Here, we demonstrate that TFE3 and miR-661 maintain the high expression level of HOXD-AS2 by regulating its production and degradation. We found that TFE3 acted as a transcription factor binding to the HOXD-AS2 promoter region and raised H3K27ac to activate HOXD-AS2. As the cytoplasmic-located lncRNA, HOXD-AS2 could be degraded by miR-661. This process was inhibited in gliomas due to the low expression of miR-661. Our study explains why HOXD-AS2 was specifically up-regulated in gliomas, helps to understand the molecular characteristics of gliomas, and provids insights for the search for specific markers in gliomas.
Highlights
IntroductionGlioma accounts for nearly 80% of primary tumors in the central nervous system
Received: 29 January 2022Glioma accounts for nearly 80% of primary tumors in the central nervous system.Glioblastoma multiforme (GBM, glioblastoma) is the most aggressive, invasive tumor of gliomas [1,2]
Genotype-Tissue Expression (GTEx) [30] data and found that HOXD-AS2 was up-regulated in glioblastomas and low-grade gliomas (LGG) compared to other cancers (Figure 1b)
Summary
Glioma accounts for nearly 80% of primary tumors in the central nervous system. Glioblastoma multiforme (GBM, glioblastoma) is the most aggressive, invasive tumor of gliomas [1,2]. Patients with glioblastomas have a poor prognosis, and only have a mean survival of 14.6 months among adults [3,4]. Some molecular features, such as isocitrate dehydrogenase 1 (IDH-1) mutation, confer a favorable prognosis [5]. IDH wild-type glioblastomas typically contain higher rates of epidermal growth factor receptor gene (EGFR) amplification and phosphatase and tensin homolog (PTEN) deletions [5–7]. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation is initially identified as a prognostic and predictive marker within the diagnosis of GBM in patients treated with temozolomide [8]. IDH mutation is thought to be followed by other mutations, such as TP53, ATRX (astrocytoma) or co-deletion of 1p/19q (oligodendroglioma) [9,10]. To improve the glioma treatment, it is essential to get a better understanding of the molecular information of gliomas and develop new therapeutic strategies
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