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HOTAIR is a therapeutic target in glioblastoma.

Zhou X, Ren Y, Zhang J, Zhang C, Zhang K, Han L, Kong L, Wei J, Chen L, Yang J, Wang Q, Zhang J, Yang Y, Jiang T, Li M, Kang C - Oncotarget (2015)

Bottom Line: An intracranial animal model was used to confirm that HOTAIR depletion inhibited GBM cell migration/invasion.In the orthotopic model, HOTAIR was required for GBM formation in vivo.In summary, HOTAIR is a potential therapeutic target in GBM.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin 300052, China.

ABSTRACT
HOTAIR is a negative prognostic factor and is overexpressed in multiple human cancers including glioblastoma multiform (GBM). Survival analysis of Chinese Glioma Genome Atlas (CGGA) patient data indicated that high HOTAIR expression was associated with poor outcome in GBM patients. NLK (Nemo-like kinase), a negative regulator of the β-catenin pathway, was negatively correlated with HOTAIR expression. When the β-catenin pathway was inhibited, GBM cells became susceptible to cell cycle arrest and inhibition of invasion. Introduction of the HOTAIR 5' domain in human glioma-derived astrocytoma induced β-catenin. An intracranial animal model was used to confirm that HOTAIR depletion inhibited GBM cell migration/invasion. In the orthotopic model, HOTAIR was required for GBM formation in vivo. In summary, HOTAIR is a potential therapeutic target in GBM.

No MeSH data available.


Related in: MedlinePlus

High levels of HOTAIR correlate with NLK expression and confer a poor prognosis in GBM patients(A) The sequencing data from HOTAIR-depleted U87 cells overlapped with that of glioma genome atlas public databases. (B) HOTAIR was highly expressed in grade IV gliomas (P < 0.05). (C) NLK was expressed at a lower level in grade III and IV gliomas (P < 0.05). (D) Pearson's correlation analysis indicated that HOTAIR expression was negatively associated with NLK expression (r = 0.156, P < 0.01). (E) Kaplan–Meier survival curve analysis indicated that GBM patients with lower HOTAIR expression showed prolonged survival compared with patients with high levels of HOTAIR (P < 0.001).
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Figure 1: High levels of HOTAIR correlate with NLK expression and confer a poor prognosis in GBM patients(A) The sequencing data from HOTAIR-depleted U87 cells overlapped with that of glioma genome atlas public databases. (B) HOTAIR was highly expressed in grade IV gliomas (P < 0.05). (C) NLK was expressed at a lower level in grade III and IV gliomas (P < 0.05). (D) Pearson's correlation analysis indicated that HOTAIR expression was negatively associated with NLK expression (r = 0.156, P < 0.01). (E) Kaplan–Meier survival curve analysis indicated that GBM patients with lower HOTAIR expression showed prolonged survival compared with patients with high levels of HOTAIR (P < 0.001).

Mentions: First, we analyzed changes in mRNA levels in HOTAIR-depleted U87 GBM cells. In total, we validated differential expression of 1,288 upregulated genes and 1,628 downregulated genes compared with cells treated with Lenti-NC virus (Figure 1A). Furthermore, we combined the mRNA sequencing data and the publically available microarray gene expression data for glioblastoma patients: 123 samples of GBM from TCGA (Agilent 4502A-1) [22], 34 samples of GBM from CGGA2 [23], 227 samples of GBM from Rembrandt [24], 79 samples of GBM from TTseq [25], and 77 samples of GBM from GSE4290 [26]. For each data cohort, Pearson correlation was used to evaluate the correlation between the expression of HOTAIR and that of other genes. A significant HOTAIR-associated gene was identified when the P value of the correlation was less than 0.05. We discovered that the expression of NLK was significantly associated with that of HOTAIR in four data cohorts except in TTseq data cohort (see Supplementary Figure S1A–S1E).


HOTAIR is a therapeutic target in glioblastoma.

Zhou X, Ren Y, Zhang J, Zhang C, Zhang K, Han L, Kong L, Wei J, Chen L, Yang J, Wang Q, Zhang J, Yang Y, Jiang T, Li M, Kang C - Oncotarget (2015)

High levels of HOTAIR correlate with NLK expression and confer a poor prognosis in GBM patients(A) The sequencing data from HOTAIR-depleted U87 cells overlapped with that of glioma genome atlas public databases. (B) HOTAIR was highly expressed in grade IV gliomas (P < 0.05). (C) NLK was expressed at a lower level in grade III and IV gliomas (P < 0.05). (D) Pearson's correlation analysis indicated that HOTAIR expression was negatively associated with NLK expression (r = 0.156, P < 0.01). (E) Kaplan–Meier survival curve analysis indicated that GBM patients with lower HOTAIR expression showed prolonged survival compared with patients with high levels of HOTAIR (P < 0.001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480757&req=5

Figure 1: High levels of HOTAIR correlate with NLK expression and confer a poor prognosis in GBM patients(A) The sequencing data from HOTAIR-depleted U87 cells overlapped with that of glioma genome atlas public databases. (B) HOTAIR was highly expressed in grade IV gliomas (P < 0.05). (C) NLK was expressed at a lower level in grade III and IV gliomas (P < 0.05). (D) Pearson's correlation analysis indicated that HOTAIR expression was negatively associated with NLK expression (r = 0.156, P < 0.01). (E) Kaplan–Meier survival curve analysis indicated that GBM patients with lower HOTAIR expression showed prolonged survival compared with patients with high levels of HOTAIR (P < 0.001).
Mentions: First, we analyzed changes in mRNA levels in HOTAIR-depleted U87 GBM cells. In total, we validated differential expression of 1,288 upregulated genes and 1,628 downregulated genes compared with cells treated with Lenti-NC virus (Figure 1A). Furthermore, we combined the mRNA sequencing data and the publically available microarray gene expression data for glioblastoma patients: 123 samples of GBM from TCGA (Agilent 4502A-1) [22], 34 samples of GBM from CGGA2 [23], 227 samples of GBM from Rembrandt [24], 79 samples of GBM from TTseq [25], and 77 samples of GBM from GSE4290 [26]. For each data cohort, Pearson correlation was used to evaluate the correlation between the expression of HOTAIR and that of other genes. A significant HOTAIR-associated gene was identified when the P value of the correlation was less than 0.05. We discovered that the expression of NLK was significantly associated with that of HOTAIR in four data cohorts except in TTseq data cohort (see Supplementary Figure S1A–S1E).

Bottom Line: An intracranial animal model was used to confirm that HOTAIR depletion inhibited GBM cell migration/invasion.In the orthotopic model, HOTAIR was required for GBM formation in vivo.In summary, HOTAIR is a potential therapeutic target in GBM.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, Tianjin Medical University General Hospital, Laboratory of Neuro-oncology, Tianjin Neurological Institute, Tianjin 300052, China.

ABSTRACT
HOTAIR is a negative prognostic factor and is overexpressed in multiple human cancers including glioblastoma multiform (GBM). Survival analysis of Chinese Glioma Genome Atlas (CGGA) patient data indicated that high HOTAIR expression was associated with poor outcome in GBM patients. NLK (Nemo-like kinase), a negative regulator of the β-catenin pathway, was negatively correlated with HOTAIR expression. When the β-catenin pathway was inhibited, GBM cells became susceptible to cell cycle arrest and inhibition of invasion. Introduction of the HOTAIR 5' domain in human glioma-derived astrocytoma induced β-catenin. An intracranial animal model was used to confirm that HOTAIR depletion inhibited GBM cell migration/invasion. In the orthotopic model, HOTAIR was required for GBM formation in vivo. In summary, HOTAIR is a potential therapeutic target in GBM.

No MeSH data available.


Related in: MedlinePlus