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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

HOTAIR inhibited NLK transcription in vitro(A) Lenti-HOTAIR si treatment induced NLK expression in U87 and U87vIII GBM cell lines after 48 h. (B) U87 and U87vIII GBM cell lines were incubated with 5 μmol/L DZNEP or 2PCPA for 48 h, and DZNEP treatment increased the level of NLK. (C) Astrocytoma cells were treated with Lenti-HOTAIR 3′ or 5′ domain for 48 h, and treatment with Lenti-HOTAIR 5′ domain inhibited NLK expression. GAPDH was used as a loading control. (D) and (E) The interaction of H3K27me3 and NLK-encoding gene regulatory elements (an approximately 5 kb region upstream from the transcriptional start site) was determined by CHIP assay.
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Figure 2: HOTAIR inhibited NLK transcription in vitro(A) Lenti-HOTAIR si treatment induced NLK expression in U87 and U87vIII GBM cell lines after 48 h. (B) U87 and U87vIII GBM cell lines were incubated with 5 μmol/L DZNEP or 2PCPA for 48 h, and DZNEP treatment increased the level of NLK. (C) Astrocytoma cells were treated with Lenti-HOTAIR 3′ or 5′ domain for 48 h, and treatment with Lenti-HOTAIR 5′ domain inhibited NLK expression. GAPDH was used as a loading control. (D) and (E) The interaction of H3K27me3 and NLK-encoding gene regulatory elements (an approximately 5 kb region upstream from the transcriptional start site) was determined by CHIP assay.

Mentions: HOTAIR knockdown induces or represses multiple genes that could contribute to the functional pro-oncogenic activity of HOTAIR in GBM. Therefore, we measured NLK expression in Lenti-HOTAIR si-treated GBM cells and found that NLK expression was significantly elevated compared with the Lenti-NC-treated cells (Figure 2A). DZNEP and 2PCPA, an EZH2 or LSD1 inhibitor that may block the function of the HOTAIR 5′ or 3′ domain, was used to further study the role of HOTAIR in regulating target gene expression. DZNEP treatment increased the expression of NLK in both U87 and U87vIII GBM cells (Figure 2B). 2PCPA treated U87 and U87vIII GBM cells showed no significant NLK expression (Figure 2B). Interestingly, introduction of the HOTAIR 5′ domain into an astrocytoma-derived primary culture dramatically decreased NLK expression, whereas the HOTAIR 3′ domain did not have this effect (Figure 2C).


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)

HOTAIR inhibited NLK transcription in vitro(A) Lenti-HOTAIR si treatment induced NLK expression in U87 and U87vIII GBM cell lines after 48 h. (B) U87 and U87vIII GBM cell lines were incubated with 5 μmol/L DZNEP or 2PCPA for 48 h, and DZNEP treatment increased the level of NLK. (C) Astrocytoma cells were treated with Lenti-HOTAIR 3′ or 5′ domain for 48 h, and treatment with Lenti-HOTAIR 5′ domain inhibited NLK expression. GAPDH was used as a loading control. (D) and (E) The interaction of H3K27me3 and NLK-encoding gene regulatory elements (an approximately 5 kb region upstream from the transcriptional start site) was determined by CHIP assay.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: HOTAIR inhibited NLK transcription in vitro(A) Lenti-HOTAIR si treatment induced NLK expression in U87 and U87vIII GBM cell lines after 48 h. (B) U87 and U87vIII GBM cell lines were incubated with 5 μmol/L DZNEP or 2PCPA for 48 h, and DZNEP treatment increased the level of NLK. (C) Astrocytoma cells were treated with Lenti-HOTAIR 3′ or 5′ domain for 48 h, and treatment with Lenti-HOTAIR 5′ domain inhibited NLK expression. GAPDH was used as a loading control. (D) and (E) The interaction of H3K27me3 and NLK-encoding gene regulatory elements (an approximately 5 kb region upstream from the transcriptional start site) was determined by CHIP assay.
Mentions: HOTAIR knockdown induces or represses multiple genes that could contribute to the functional pro-oncogenic activity of HOTAIR in GBM. Therefore, we measured NLK expression in Lenti-HOTAIR si-treated GBM cells and found that NLK expression was significantly elevated compared with the Lenti-NC-treated cells (Figure 2A). DZNEP and 2PCPA, an EZH2 or LSD1 inhibitor that may block the function of the HOTAIR 5′ or 3′ domain, was used to further study the role of HOTAIR in regulating target gene expression. DZNEP treatment increased the expression of NLK in both U87 and U87vIII GBM cells (Figure 2B). 2PCPA treated U87 and U87vIII GBM cells showed no significant NLK expression (Figure 2B). Interestingly, introduction of the HOTAIR 5′ domain into an astrocytoma-derived primary culture dramatically decreased NLK expression, whereas the HOTAIR 3′ domain did not have this effect (Figure 2C).

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