Upregulation of DLX2 Confers a Poor Prognosis in Glioblastoma Patients by Inducing a Proliferative Phenotype

Abstract

The human Distal-less Homeobox (DLX) gene family encodes homeobox transcription factors involved in the control of morphogenesis and tissue homeostasis, which is primarily expressed in embryonic development. Recently, DLX gene family was reported to have essential roles in carcinogenesis. We have profiled whole genome expressed genes in 83 glioblastoma multiforme (GBM) patients from the Chinese Glioma Genome Atlas (CGGA) Group. Two major groups of samples were identified in mRNA expression profiles (referred to as Cluster 1 (C1) and Cluster 2 (C2)). We identified 7 out of the top 10 Gene Ontology terms in the C1 group were associated with differentiation and development of neuronal cell. The most significant prognostic gene was DLX2 (P < 0.001, OR = 1.744); overexpression of DLX2 indicated poor survival in the 83 GBM patients (low DLX2 vs high DLX2, 77.6 vs 44.7 weeks, P < 0.001). Annotation of mRNA profiling data on GBM from The Cancer Genome Atlas and MD Anderson Cancer Center showed the proneural and neural subtypes highly correlated with low and high DLX2 expression, respectively. Knocking down of DLX2 in GBM cell line-LN229 results in decreased cyclin D1 expression and cell proliferation. Collectively, these data identified high expression of DLX2 as a poor prognostic marker to GBM patients.

Long non-coding RNA TUG1 promotes cell progression in hepatocellular carcinoma via regulating miR-216b-5p/DLX2 axis

“…The distal-free homeobox (DLX) gene family has been supported to be involved in a lot of physiological and pathological events [34]. Among them, DLX2 plays a crucial role in the development of many human cancers, including glioma and gastric adenocarcinoma cancers [35,36]. A previous study showed that DLX2 promoted the proliferation of HCC cells [23].…”

A gain-of-function senescence bypass screen identifies the homeobox transcription factor DLX2 as a regulator of ATM–p53 signaling

“…DLX2 has been reported to be involved in embryonic brain, retina, and craniofacial development (de Melo et al 2005(de Melo et al , 2008Petryniak et al 2007;Gordon et al 2010). In addition to its role in development, high DLX2 expression has been found in a variety of cancers (Yilmaz et al 2011), and studies have shown that DLX2 expression associates with poor prognosis in glioblastoma and gastric cancer (Tang et al 2013;Yan et al 2013). A recent study found that DLX2 is involved in regulating TGF-β-induced growth arrest, and loss of DLX2 inhibits melanoma tumor growth and metastasis in mouse models (Yilmaz et al 2011).…”

Overexpression of DLX2 is associated with poor prognosis and sorafenib resistance in hepatocellular carcinoma

“…DLX2 is a member of the DLX family that reportedly participates in tumour progression. DLX2 is a marker of poor prognosis in patients with glioma and its overexpression increases Cyclin D1 expression and cell proliferation (Yan et al, 2013). Increased DLX2 expression may correlate with advanced stage in patients with gastric adenocarcinoma and contribute to tumour development (Tang et al, 2013).…”