Homeobox C9 suppresses Beclin1-mediated autophagy in glioblastoma by directly inhibiting the transcription of death-associated protein kinase 1

Fan Xuan, Mengying Huang, Wen Liu, Hanfei Ding, Liqun Yang, Hongjuan Cui

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background The transcription factor homeobox C9 (HOXC9) plays a crucial role in developmental regulatory systems, where it determines the specific positional identities of cells along the anteroposterior axis. The expression of HOXC9 has been found to be dysregulated in some cancers such as lung cancer, breast cancer, and neuroblastoma. Here, we report for the first time that HOXC9 is a novel autophagy regulator and reveal its oncogenic role in cell survival and its usefulness as a prognostic marker in glioblastoma patients. Methods Kaplan-Meier analysis was performed to evaluate the possible prognostic value of HOXC9 in glioblastoma. Growth curve assays, subcutaneous, and orthotopic implantations were used to analyze cell viability and tumor formation, respectively. Luciferase and chromatin immunoprecipitation assays were employed to explore the mechanisms involved in the association between HOXC9 and its downstream effector, death-associated protein kinase 1 (DAPK1). Results High expression of HOXC9 was found to be an indicator of a poor prognosis in glioblastoma. HOXC9 knockdown resulted in a significant reduction of cell viability, migration, invasion, and tumorigenicity and a marked increase in autophagy. During the autophagy process, HOXC9 inhibited DAPK1 transcription by directly binding to its promoter. The downregulation of HOXC9 releases its transcriptional inhibition of DAPK1, resulting in the activation of the DAPK1-Beclin1 pathway, which induces autophagy in glioblastoma cells. Conclusions Collectively, our data indicate that HOXC9 is an oncogene in glioblastoma. We have revealed its role in the control of autophagy, and we suggest that HOXC9 is a novel and promising therapeutic target.

Original languageEnglish (US)
Pages (from-to)819-829
Number of pages11
JournalNeuro-Oncology
Volume18
Issue number6
DOIs
StatePublished - Jun 10 2016

Fingerprint

Death-Associated Protein Kinases
Homeobox Genes
Autophagy
Glioblastoma
Cell Survival
Beclin-1
Breast Neoplasms
Chromatin Immunoprecipitation
Kaplan-Meier Estimate
Luciferases
Neuroblastoma
Oncogenes
Cell Movement

Keywords

  • DAPK1
  • HOXC9
  • autophagy
  • glioblastoma
  • tumorigenesis

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

Cite this

Homeobox C9 suppresses Beclin1-mediated autophagy in glioblastoma by directly inhibiting the transcription of death-associated protein kinase 1. / Xuan, Fan; Huang, Mengying; Liu, Wen; Ding, Hanfei; Yang, Liqun; Cui, Hongjuan.

In: Neuro-Oncology, Vol. 18, No. 6, 10.06.2016, p. 819-829.

Research output: Contribution to journalArticle

Xuan, Fan ; Huang, Mengying ; Liu, Wen ; Ding, Hanfei ; Yang, Liqun ; Cui, Hongjuan. / Homeobox C9 suppresses Beclin1-mediated autophagy in glioblastoma by directly inhibiting the transcription of death-associated protein kinase 1. In: Neuro-Oncology. 2016 ; Vol. 18, No. 6. pp. 819-829.
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AU - Yang, Liqun

AU - Cui, Hongjuan

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N2 - Background The transcription factor homeobox C9 (HOXC9) plays a crucial role in developmental regulatory systems, where it determines the specific positional identities of cells along the anteroposterior axis. The expression of HOXC9 has been found to be dysregulated in some cancers such as lung cancer, breast cancer, and neuroblastoma. Here, we report for the first time that HOXC9 is a novel autophagy regulator and reveal its oncogenic role in cell survival and its usefulness as a prognostic marker in glioblastoma patients. Methods Kaplan-Meier analysis was performed to evaluate the possible prognostic value of HOXC9 in glioblastoma. Growth curve assays, subcutaneous, and orthotopic implantations were used to analyze cell viability and tumor formation, respectively. Luciferase and chromatin immunoprecipitation assays were employed to explore the mechanisms involved in the association between HOXC9 and its downstream effector, death-associated protein kinase 1 (DAPK1). Results High expression of HOXC9 was found to be an indicator of a poor prognosis in glioblastoma. HOXC9 knockdown resulted in a significant reduction of cell viability, migration, invasion, and tumorigenicity and a marked increase in autophagy. During the autophagy process, HOXC9 inhibited DAPK1 transcription by directly binding to its promoter. The downregulation of HOXC9 releases its transcriptional inhibition of DAPK1, resulting in the activation of the DAPK1-Beclin1 pathway, which induces autophagy in glioblastoma cells. Conclusions Collectively, our data indicate that HOXC9 is an oncogene in glioblastoma. We have revealed its role in the control of autophagy, and we suggest that HOXC9 is a novel and promising therapeutic target.

AB - Background The transcription factor homeobox C9 (HOXC9) plays a crucial role in developmental regulatory systems, where it determines the specific positional identities of cells along the anteroposterior axis. The expression of HOXC9 has been found to be dysregulated in some cancers such as lung cancer, breast cancer, and neuroblastoma. Here, we report for the first time that HOXC9 is a novel autophagy regulator and reveal its oncogenic role in cell survival and its usefulness as a prognostic marker in glioblastoma patients. Methods Kaplan-Meier analysis was performed to evaluate the possible prognostic value of HOXC9 in glioblastoma. Growth curve assays, subcutaneous, and orthotopic implantations were used to analyze cell viability and tumor formation, respectively. Luciferase and chromatin immunoprecipitation assays were employed to explore the mechanisms involved in the association between HOXC9 and its downstream effector, death-associated protein kinase 1 (DAPK1). Results High expression of HOXC9 was found to be an indicator of a poor prognosis in glioblastoma. HOXC9 knockdown resulted in a significant reduction of cell viability, migration, invasion, and tumorigenicity and a marked increase in autophagy. During the autophagy process, HOXC9 inhibited DAPK1 transcription by directly binding to its promoter. The downregulation of HOXC9 releases its transcriptional inhibition of DAPK1, resulting in the activation of the DAPK1-Beclin1 pathway, which induces autophagy in glioblastoma cells. Conclusions Collectively, our data indicate that HOXC9 is an oncogene in glioblastoma. We have revealed its role in the control of autophagy, and we suggest that HOXC9 is a novel and promising therapeutic target.

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