HOXA13 is a potential GBM diagnostic marker and promotes glioma invasion by activating the Wnt and TGF-β pathways

Duan, Ran; Han, Lei; Wang, Qixue; Wei, Jianwei; Chen, Luyue; Zhang, Jianning; Kang, Chunsheng; Wang, Lei

doi:10.18632/oncotarget.4813

Cited by 85 publications

(74 citation statements)

References 36 publications

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“…Multiple HOX genes have been shown to be overexpressed in glioma and confer prognostic value [30, 35], while HOXA10 has been shown to play a role in drug resistance and tumor recurrence [36]. In the present study, we found that HOXA5, HOXA7, HOXA10, HOXC4 and HOXC6 are prognostic markers in glioma patients.…”

Section: Discussionsupporting

confidence: 56%

CD133 in brain tumor: the prognostic factor

McCrudden

Yuen

et al. 2016

Oncotarget

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CD133 has been shown to be an important stem cell factor that promotes glioma progression. However, the mechanism for CD133-mediated glioma progression has yet to be fully elucidated. In this study, we found that CD133 mRNA expression was a prognostic marker in three independent glioma patient cohorts, corroborating a putative role for CD133 in glioma progression. Importantly, we found that CD133 expression in glioma was highly correlated with the expression of HOX gene stem cell factors (HOXA5, HOXA7, HOXA10, HOXC4 and HOXC6). The expression of these HOX genes individually was significantly associated with survival. Interestingly, the prognostic significance of CD133 was dependent on the expression level of HOX genes, and vice versa. CD133 (p = 0.021) and HOXA7 (p = 0.001) were independent prognostic markers when the three glioma patient cohorts were combined (n = 231). Our results suggest that HOX genes may play a more important role in progression of glioma when CD133 expression is low. Furthermore, we showed that low-level expression of LIM2 in CD133-high glioma was associated with poorer survival, suggesting that LIM2 could be a therapeutic target for glioma expressing a high level of CD133. Connectivity mapping identified vinblastine and vincristine as agents that could reverse the CD133/HOX genes/LIM2-signature, and we confirmed this by in vitro analysis in glioma cell lines, demonstrating that CD133 and HOX genes were co-expressed and could be downregulated by vincristine. In conclusion, our data show that CD133 and HOX genes are important prognostic markers in glioma and shed light on possible treatment strategies for glioma expressing a high level of CD133.

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Section: Discussionsupporting

confidence: 56%

CD133 in brain tumor: the prognostic factor

McCrudden

Yuen

et al. 2016

Oncotarget

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“…Interfering with such pathways has been shown to affect MT in GBMs. As such, WNT signaling controls GBM invasion at least in part through the initiation of MT (Bhuvanalakshmi et al, 2015;Duan et al, 2015;Jin et al, 2011;Kahlert et al, 2012). Forkhead box M1 (FoxM1) promotes glioma tumorigenicity through the WNT pathway partly by inducing EMT (Wang et al, 2015a;Zhang et al, 2011).…”

Section: Mt In Maintenance Of Neural and Gbm Stem Cellsmentioning

confidence: 99%

EMT‐ and MET‐related processes in nonepithelial tumors: importance for disease progression, prognosis, and therapeutic opportunities

2017

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The epithelial‐to mesenchymal (EMT) process is increasingly recognized for playing a key role in the progression, dissemination, and therapy resistance of epithelial tumors. Accumulating evidence suggests that EMT inducers also lead to a gain in mesenchymal properties and promote malignancy of nonepithelial tumors. In this review, we present and discuss current findings, illustrating the importance of EMT inducers in tumors originating from nonepithelial/mesenchymal tissues, including brain tumors, hematopoietic malignancies, and sarcomas. Among these tumors, the involvement of mesenchymal transition has been most extensively investigated in glioblastoma, providing proof for cell autonomous and microenvironment‐derived stimuli that provoke EMT‐like processes that regulate stem cell, invasive, and immunogenic properties as well as therapy resistance. The involvement of prominent EMT transcription factor families, such as TWIST, SNAI, and ZEB, in promoting therapy resistance and tumor aggressiveness has also been reported in lymphomas, leukemias, and sarcomas. A reverse process, resembling mesenchymal‐to‐epithelial transition (MET), seems particularly relevant for sarcomas, where (partial) epithelial differentiation is linked to less aggressive tumors and a better patient prognosis. Overall, a hybrid model in which more stable epithelial and mesenchymal intermediates exist likely extends to the biology of tumors originating from sources other than the epithelium. Deeper investigation and understanding of the EMT/MET machinery in nonepithelial tumors will shed light on the pathogenesis of these tumors, potentially paving the way toward the identification of clinically relevant biomarkers for prognosis and future therapeutic targets.

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“…Thus, to investigate the binding motifs between TFs and lncRNAs, we performed motif searching analysis to the DNA regulatory elements of all lncRNAs. 32 In the promoter regions, PLAG1, HOXA13 and POU2F1 also had the most binding sites and bound the majority of lncRNAs ( Figure 6B). Hub genes often play important roles in the biological processes, so we extracted the motif searching results of 12 hub TFs.…”

Section: Identification Of Core Lncrna-tf Crosstalksmentioning

confidence: 96%

“…Downregulation of HOXA13 resulted in decreased tumor growth. 32 In the promoter regions, PLAG1, HOXA13 and POU2F1 also had the most binding sites and bound the majority of lncRNAs ( Figure 6B). All these results implied that hub TFs might function as core TFs that bind the enhancers and promoters of abundant lncRNAs and form the "feedback loops" to participate in cancer biology ( Figure 6C).…”

Section: Identification Of Core Lncrna-tf Crosstalksmentioning

confidence: 96%

Comprehensive analysis of lncRNA‐TF crosstalks and identification of prognostic regulatory feedback loops of glioblastoma using lncRNA/TF‐mediated ceRNA network

Hong

et al. 2019

J of Cellular Biochemistry

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Glioblastoma (GBM) has become the most aggressive primary brain tumor in the world. Patients with GBM usually have a poor prognosis. The median survival times of GBM patients retain less than 2 years. Thus, it is urgent to investigate the molecular mechanism of GBM. Recently, studies have demonstrated that transcription factors (TFs) participate in cancer pathology by regulating long noncoding RNAs (lncRNAs). However, the functional and regulatory roles of TF‐lncRNA crosstalks are still unclear. In this study, we constructed a global lncRNA‐TF network (GLTN) based on competing endogenous RNA. As a result, some topological features of GLTN were identified. A known GBM lncRNA MCM3AP‐AS1 showed multiple central topological features in GLTN. Furthermore, we identified hub genes and extracted the hub‐hub pairs from GLTN to form a hub associated lncRNA‐TF network (HALTN). Results showed that a risk model combined with multiple hubs had a significant effect on prognosis. Additionally, we performed module searching and two functional modules from HALTN were identified, which were confirmed as risk factors of GBM. More importantly, we also identified some core lncRNA‐TF crosstalks that might form feedback loops to control the biological processes in GBM. Our results demonstrated that the synergistic, competitive lncRNA‐TF crosstalks played an important role in pathological processes of GBM, and had strong effect on prognosis. All these results can help us to uncover the molecular mechanism and provide a new therapeutic target for GBM.

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HOXA13 is a potential GBM diagnostic marker and promotes glioma invasion by activating the Wnt and TGF-β pathways

Cited by 85 publications

References 36 publications

CD133 in brain tumor: the prognostic factor

CD133 in brain tumor: the prognostic factor

EMT‐ and MET‐related processes in nonepithelial tumors: importance for disease progression, prognosis, and therapeutic opportunities

Comprehensive analysis of lncRNA‐TF crosstalks and identification of prognostic regulatory feedback loops of glioblastoma using lncRNA/TF‐mediated ceRNA network

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