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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 regulated GBM invasion in vitro(A) A 3D matrigel assay indicated that Lenti-HOTAIR si inhibited proliferation and the ability to dehydrate ECM in U87 and U87vIII cells (P < 0.05). (B) Transwell assays indicated that Lenti-HOTAIR si inhibited invasion of U87 and U87vIII cells (P < 0.05). (C) Wound healing assays indicated that Lenti-HOTAIR si inhibited cell migration in U87 and U87vIII cells (P < 0.05). (D) Lenti-HOTAIR si treatment induced E-cadherin expression and inhibited the expression of N-cadherin, NF-κB, Slug, Zeb-1 and Twist-1 in MCF-7, U87 and U87vIII cells. (E) DZNEP treatment induced E-cadherin expression and inhibited N-cadherin, NF-κB, Zeb-1 and Slug expression in U87 and U87vIII cells. (F) Treatment with Lenti-HOTAIR 5′ domain inhibited E-cadherin expression while inducing N-cadherin and Slug expression in an astrocytoma primary culture. GAPDH was used as a loading control. (G) Immunofluorescence staining showed that treatment with Lenti-HOTAIR si inhibited cytoplasmic N-cadherin levels in MCF-7, U87 and U87vIII cells. F-actin staining showed a stress-fiber pattern in Lenti-NC-treated cells and a cortical pattern in Lenti-HOTAIR si-treated cells (magnification: 1000x).
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Figure 5: HOTAIR regulated GBM invasion in vitro(A) A 3D matrigel assay indicated that Lenti-HOTAIR si inhibited proliferation and the ability to dehydrate ECM in U87 and U87vIII cells (P < 0.05). (B) Transwell assays indicated that Lenti-HOTAIR si inhibited invasion of U87 and U87vIII cells (P < 0.05). (C) Wound healing assays indicated that Lenti-HOTAIR si inhibited cell migration in U87 and U87vIII cells (P < 0.05). (D) Lenti-HOTAIR si treatment induced E-cadherin expression and inhibited the expression of N-cadherin, NF-κB, Slug, Zeb-1 and Twist-1 in MCF-7, U87 and U87vIII cells. (E) DZNEP treatment induced E-cadherin expression and inhibited N-cadherin, NF-κB, Zeb-1 and Slug expression in U87 and U87vIII cells. (F) Treatment with Lenti-HOTAIR 5′ domain inhibited E-cadherin expression while inducing N-cadherin and Slug expression in an astrocytoma primary culture. GAPDH was used as a loading control. (G) Immunofluorescence staining showed that treatment with Lenti-HOTAIR si inhibited cytoplasmic N-cadherin levels in MCF-7, U87 and U87vIII cells. F-actin staining showed a stress-fiber pattern in Lenti-NC-treated cells and a cortical pattern in Lenti-HOTAIR si-treated cells (magnification: 1000x).

Mentions: HOTAIR has been characterized as a molecule involved in cancer cell invasion. Consistent with these findings, our research revealed that HOTAIR is involved in GBM cell ECM function. Consequently, we determined HOTAIR regulates the ability of GBM cells to migrate and invade by evaluating EMT-related markers, including E/N-cadherin and etc. The clone diameter of HOTAIR depleted U87 and U87vIII cell was smaller than the Lenti-NC treated cells (Figure 5A). Lenti-HOTAIR si treatment decreased the number of both U87 and U87vIII cells that migrated through the Transwell membrane by 50% compared with Lenti-NC treated cells (Figure 5B). Inhibition of HOTAIR decreased U87 and U87vIII cell migration, as shown by wound healing assays (Figure 5C). In addition, Lenti-HOTAIR si treatment increased E-cadherin expression by 2-fold and decreased N-cadherin at the protein level (Figure 5D). Accordingly, DZNEP treatment induced similar alterations in E/N-cadherin, Zeb-1, Slug and NF-κB (Figure 5E). In contrast, 2-PCPA did not affect EMT markers. We also employed a gain-of-function method to further analyze the role of HOTAIR in GBM cell invasion. Expression of the 5′ domain of HOTAIR introduced into astrocytoma cells induced N-cadherin and Slug expression and suppressed E-cadherin expression. However, expression of the HOTAIR 3′ domain did not affect the expression of EMT markers in GBM cells (Figure 5F).


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 regulated GBM invasion in vitro(A) A 3D matrigel assay indicated that Lenti-HOTAIR si inhibited proliferation and the ability to dehydrate ECM in U87 and U87vIII cells (P < 0.05). (B) Transwell assays indicated that Lenti-HOTAIR si inhibited invasion of U87 and U87vIII cells (P < 0.05). (C) Wound healing assays indicated that Lenti-HOTAIR si inhibited cell migration in U87 and U87vIII cells (P < 0.05). (D) Lenti-HOTAIR si treatment induced E-cadherin expression and inhibited the expression of N-cadherin, NF-κB, Slug, Zeb-1 and Twist-1 in MCF-7, U87 and U87vIII cells. (E) DZNEP treatment induced E-cadherin expression and inhibited N-cadherin, NF-κB, Zeb-1 and Slug expression in U87 and U87vIII cells. (F) Treatment with Lenti-HOTAIR 5′ domain inhibited E-cadherin expression while inducing N-cadherin and Slug expression in an astrocytoma primary culture. GAPDH was used as a loading control. (G) Immunofluorescence staining showed that treatment with Lenti-HOTAIR si inhibited cytoplasmic N-cadherin levels in MCF-7, U87 and U87vIII cells. F-actin staining showed a stress-fiber pattern in Lenti-NC-treated cells and a cortical pattern in Lenti-HOTAIR si-treated cells (magnification: 1000x).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: HOTAIR regulated GBM invasion in vitro(A) A 3D matrigel assay indicated that Lenti-HOTAIR si inhibited proliferation and the ability to dehydrate ECM in U87 and U87vIII cells (P < 0.05). (B) Transwell assays indicated that Lenti-HOTAIR si inhibited invasion of U87 and U87vIII cells (P < 0.05). (C) Wound healing assays indicated that Lenti-HOTAIR si inhibited cell migration in U87 and U87vIII cells (P < 0.05). (D) Lenti-HOTAIR si treatment induced E-cadherin expression and inhibited the expression of N-cadherin, NF-κB, Slug, Zeb-1 and Twist-1 in MCF-7, U87 and U87vIII cells. (E) DZNEP treatment induced E-cadherin expression and inhibited N-cadherin, NF-κB, Zeb-1 and Slug expression in U87 and U87vIII cells. (F) Treatment with Lenti-HOTAIR 5′ domain inhibited E-cadherin expression while inducing N-cadherin and Slug expression in an astrocytoma primary culture. GAPDH was used as a loading control. (G) Immunofluorescence staining showed that treatment with Lenti-HOTAIR si inhibited cytoplasmic N-cadherin levels in MCF-7, U87 and U87vIII cells. F-actin staining showed a stress-fiber pattern in Lenti-NC-treated cells and a cortical pattern in Lenti-HOTAIR si-treated cells (magnification: 1000x).
Mentions: HOTAIR has been characterized as a molecule involved in cancer cell invasion. Consistent with these findings, our research revealed that HOTAIR is involved in GBM cell ECM function. Consequently, we determined HOTAIR regulates the ability of GBM cells to migrate and invade by evaluating EMT-related markers, including E/N-cadherin and etc. The clone diameter of HOTAIR depleted U87 and U87vIII cell was smaller than the Lenti-NC treated cells (Figure 5A). Lenti-HOTAIR si treatment decreased the number of both U87 and U87vIII cells that migrated through the Transwell membrane by 50% compared with Lenti-NC treated cells (Figure 5B). Inhibition of HOTAIR decreased U87 and U87vIII cell migration, as shown by wound healing assays (Figure 5C). In addition, Lenti-HOTAIR si treatment increased E-cadherin expression by 2-fold and decreased N-cadherin at the protein level (Figure 5D). Accordingly, DZNEP treatment induced similar alterations in E/N-cadherin, Zeb-1, Slug and NF-κB (Figure 5E). In contrast, 2-PCPA did not affect EMT markers. We also employed a gain-of-function method to further analyze the role of HOTAIR in GBM cell invasion. Expression of the 5′ domain of HOTAIR introduced into astrocytoma cells induced N-cadherin and Slug expression and suppressed E-cadherin expression. However, expression of the HOTAIR 3′ domain did not affect the expression of EMT markers in GBM cells (Figure 5F).

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