Transcriptional profiling of HOXA9-regulated genes in human glioblastoma cell models

Abstract

The data here described pertain to the article by Pojo et al. (2015) [10] titled “A transcriptomic signature mediated by HOXA9 promotes human glioblastoma initiation, aggressiveness and resistance to temozolomide” (Pojo et al., 2015 [10]). HOX genes are part of the homeobox gene family, which encodes transcription factors crucial during embryonic development (Grier et al., 2005; Pearson et al., 2005 [6], [9]) and also in postdevelopmental regulation (Neville et al., 2002; Yamamoto et al., 2003; Takahashi et al., 2004; Morgan 2006 [8], [14], [13], [7]). Alterations interfering with the regulation of these genes may lead to tumorigenesis in adults. Due to their contributions in the control of important cellular processes, the deregulation of HOX genes is ultimately correlated with cancer treatment failure and patients' poor prognosis (Golub et al., 1999; Abdel-Fattah et al., 2006 [5], [1]; Costa et al., 2010 [4]; Pojo et al., 2015 [10]). Recently, our studies showed that HOXA9 overexpression is associated with poor prognosis in patients with glioblastoma (GBM), the most common and most malignant primary brain tumor. Mechanistically, HOXA9 is associated with resistance to chemotherapy and with pro-proliferative, pro-invasive and anti-apoptotic features (Costa et al., 2010 [4]; Pojo et al., 2015 [10]) in GBM in vitro models. Since HOXA9 is a transcription factor, its target genes can be the true biological effectors of its aggressiveness. In this context, whole genome Agilent's microarrays were used to obtain the full transcriptome of HOXA9 in a variety of GBM cell models, including human immortalized astrocytes, established GBM cell lines, and GBM patient-derived cell cultures. Here, we provide detailed methods, including experimental design and microarray data analyses, which can be accessed in Gene Expression Omnibus (GEO) under the accession number GSE56517. Additional interpretation of the data is included and supplemented in (Pojo et al., 2015 [10]).

The long non-coding RNAHOTAIRis transcriptionally activated by HOXA9 and is an independent prognostic marker in patients with malignant glioma

“…Previously published transcriptomic data from our group (GEO accession number GSE56517) [ 26 , 27 ] suggested a possible regulation of HOTAIR by the homeoprotein HOXA9, an important protein in the aggressiveness, chemotherapy resistance, and prognosis of GBM [ 21 , 26 , 28 , 29 ]. Specifically, GBM cell lines with overexpression or silencing of HOXA9 presented increased or reduced expression of HOTAIR , respectively; raising the hypothesis that HOXA9 may directly regulate HOTAIR expression.…”

The expression of HOXA9 and its prognostic value in cervical cancer

“…expression in clinical specimens of ovarian cancer was strongly associated with increased abundance of tumor-associated macrophages (TAMs) and intratumoral T-regulatory cells [22]. Céline S. Gonçalves et al as well as Marta Pojo et al identifed HOXA9 as a critical oncogene in the initiation and progression of glioma that establish HOXA9 as a driver of glioma initiation, aggressiveness and resistance to therapy [23,24]. John Wrangle et al de ned a three-gene panel, CDO1, HOXA9, and TAC1, which degree of sensitivity and speci city may be of high value to diagnose the earliest stages of NSCLC [25].…”

Differential Expression of HOX Genes in Mesenchymal Stem Cells from Osteoarthritic Patients Is Independent of Their Promoter Methylation

“…Further chromatin immunoprecipitation analysis (ChIP) revealed the direct interaction between HOXC8 and the osteopontin promoter (OPN) and, subsequently, reduced OPN expression, confirming that OPN is a HOXC8 direct target [30]. Similarly, other authors have shown that HOXA9 overexpression is able to induce the expression of genes associated with the establishment of typical stemness characteristics, such as invasive potential, migration, etc., properties that can be reverted after HOXA9 silencing [31]. Collectively, these pieces of evidence seem to indicate that OA-MSCs have a partial loss of their stemness and simultaneously adopt a phenotype with typical characteristics of bone tissue.…”