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HOXB1 Is a Tumor Suppressor Gene Regulated by miR-3175 in Glioma.

Han L, Liu D, Li Z, Tian N, Han Z, Wang G, Fu Y, Guo Z, Zhu Z, Du C, Tian Y - PLoS ONE (2015)

Bottom Line: The HOXB1 gene plays a critical role as an oncogene in diverse tumors.We show that HOXB1 expression is significantly downregulated in glioma tissues and cell lines, and that its expression may be closely associated with the degree of malignancy.Our results suggest that HOXB1 functions as a tumor suppressor, regulated by miR-3175 in glioma.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.

ABSTRACT
The HOXB1 gene plays a critical role as an oncogene in diverse tumors. However, the functional role of HOXB1 and the mechanism regulating HOXB1 expression in glioma are not fully understood. A preliminary bioinformatics analysis showed that HOXB1 is ectopically expressed in glioma, and that HOXB1 is a possible target of miR-3175. In this study, we investigated the function of HOXB1 and the relationship between HOXB1 and miR-3175 in glioma. We show that HOXB1 expression is significantly downregulated in glioma tissues and cell lines, and that its expression may be closely associated with the degree of malignancy. Reduced HOXB1 expression promoted the proliferation and invasion of glioma cells, and inhibited their apoptosis in vitro, and the downregulation of HOXB1 was also associated with worse survival in glioma patients. More importantly, HOXB1 was shown experimentally to be a direct target of miR-3175 in this study. The downregulated expression of miR-3175 inhibited cell proliferation and invasion, and promoted apoptosis in glioma. The oncogenicity induced by low HOXB1 expression was prevented by an miR-3175 inhibitor in glioma cells. Our results suggest that HOXB1 functions as a tumor suppressor, regulated by miR-3175 in glioma. These results clarify the pathogenesis of glioma and offer a potential target for its treatment.

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Related in: MedlinePlus

HOXB1 downregulation is associated with poor survival.Kaplan-Meier life table method analysis indicated (A-B) that patients with low HOXB1 expression have significantly shorter OS and PFS.
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pone.0142387.g002: HOXB1 downregulation is associated with poor survival.Kaplan-Meier life table method analysis indicated (A-B) that patients with low HOXB1 expression have significantly shorter OS and PFS.

Mentions: We evaluated the prognostic value of HOXB1 expression for patient OS and PFS based on the follow-up data of glioma patients. OS and PFS were stratified by HOXB1 expression using the Kaplan-Meier life table method and Cox regression models. In this study, we found that high HOXB1 expression predicted longer OS and PFS (Fig 2A and 2B). Univariate Cox regression models showed that only HOXB1 expression (hazards ratio [HR] 0.055, P = 0.004, 95% confidence interval [95% CI] 0.008–0.394) was associated with worse survival in this prospective cohort of glioma patients (Table 1). However, glioma grade (HR 2.975, P = 0.001, 95% CI 1.702–5.201), and HOXB1 expression (HR 0.111, P = 0.001, 95% CI 0.032–0.389) were associated with the progression of glioma. A multivariate analysis showed that HOXB1 expression (HR 0.030, P = 0.001, 95% CI 0.004–0.261) and glioma grade (HR 4.682, P = 0.021, 95% CI 1.257–17.439) were associated with shorter survival (Table 2). The variables glioma grade (HR 2.732, P = 0.001, 95% CI 1.544–5.833) and HOXB1 expression (HR 0.126, P = 0.004, 95% CI 0.031–0.511) were associated with PFS. In the Cox regression analysis, the low expression level of HOXB1 was an independent predictor of poor prognosis in glioma patients. These data support the notion that low HOXB1 expression is associated with worse survival in glioma patients and may act as a tumor biomarker in malignant glioma.


HOXB1 Is a Tumor Suppressor Gene Regulated by miR-3175 in Glioma.

Han L, Liu D, Li Z, Tian N, Han Z, Wang G, Fu Y, Guo Z, Zhu Z, Du C, Tian Y - PLoS ONE (2015)

HOXB1 downregulation is associated with poor survival.Kaplan-Meier life table method analysis indicated (A-B) that patients with low HOXB1 expression have significantly shorter OS and PFS.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4643923&req=5

pone.0142387.g002: HOXB1 downregulation is associated with poor survival.Kaplan-Meier life table method analysis indicated (A-B) that patients with low HOXB1 expression have significantly shorter OS and PFS.
Mentions: We evaluated the prognostic value of HOXB1 expression for patient OS and PFS based on the follow-up data of glioma patients. OS and PFS were stratified by HOXB1 expression using the Kaplan-Meier life table method and Cox regression models. In this study, we found that high HOXB1 expression predicted longer OS and PFS (Fig 2A and 2B). Univariate Cox regression models showed that only HOXB1 expression (hazards ratio [HR] 0.055, P = 0.004, 95% confidence interval [95% CI] 0.008–0.394) was associated with worse survival in this prospective cohort of glioma patients (Table 1). However, glioma grade (HR 2.975, P = 0.001, 95% CI 1.702–5.201), and HOXB1 expression (HR 0.111, P = 0.001, 95% CI 0.032–0.389) were associated with the progression of glioma. A multivariate analysis showed that HOXB1 expression (HR 0.030, P = 0.001, 95% CI 0.004–0.261) and glioma grade (HR 4.682, P = 0.021, 95% CI 1.257–17.439) were associated with shorter survival (Table 2). The variables glioma grade (HR 2.732, P = 0.001, 95% CI 1.544–5.833) and HOXB1 expression (HR 0.126, P = 0.004, 95% CI 0.031–0.511) were associated with PFS. In the Cox regression analysis, the low expression level of HOXB1 was an independent predictor of poor prognosis in glioma patients. These data support the notion that low HOXB1 expression is associated with worse survival in glioma patients and may act as a tumor biomarker in malignant glioma.

Bottom Line: The HOXB1 gene plays a critical role as an oncogene in diverse tumors.We show that HOXB1 expression is significantly downregulated in glioma tissues and cell lines, and that its expression may be closely associated with the degree of malignancy.Our results suggest that HOXB1 functions as a tumor suppressor, regulated by miR-3175 in glioma.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurosurgery, China-Japan Union Hospital of Jilin University, Changchun, Jilin, China.

ABSTRACT
The HOXB1 gene plays a critical role as an oncogene in diverse tumors. However, the functional role of HOXB1 and the mechanism regulating HOXB1 expression in glioma are not fully understood. A preliminary bioinformatics analysis showed that HOXB1 is ectopically expressed in glioma, and that HOXB1 is a possible target of miR-3175. In this study, we investigated the function of HOXB1 and the relationship between HOXB1 and miR-3175 in glioma. We show that HOXB1 expression is significantly downregulated in glioma tissues and cell lines, and that its expression may be closely associated with the degree of malignancy. Reduced HOXB1 expression promoted the proliferation and invasion of glioma cells, and inhibited their apoptosis in vitro, and the downregulation of HOXB1 was also associated with worse survival in glioma patients. More importantly, HOXB1 was shown experimentally to be a direct target of miR-3175 in this study. The downregulated expression of miR-3175 inhibited cell proliferation and invasion, and promoted apoptosis in glioma. The oncogenicity induced by low HOXB1 expression was prevented by an miR-3175 inhibitor in glioma cells. Our results suggest that HOXB1 functions as a tumor suppressor, regulated by miR-3175 in glioma. These results clarify the pathogenesis of glioma and offer a potential target for its treatment.

Show MeSH
Related in: MedlinePlus