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Downregulation of KDM4A Suppresses the Survival of Glioma Cells by Promoting Autophagy

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Abstract

Glioma is the most common type of primary intracranial tumor and has a poor prognosis. It has been reported that lysine-specific demethylase 4A (KDM4A) can promote tumor progression; however, its role in human glioma remains unclear. Western blot and qRT-PCR analyses showed that KDM4A was highly expressed in U87MG and T98G cells. 48 h after transfection with siKDM4A, the protein level of KDM4A was significantly downregulated. The silenced expression of KDM4A in T98G or U87MG cells inhibited cell viability and invasion, and aggravated cell apoptosis. We found that the siKDM4A led to a significant increase in acidic vesicular organelles (AVOs) and upregulated the expression of autophagy-related proteins, including LC3B-phosphatidylethanolamine conjugate, a cytosolic form of LC3B (LC3B-II/LC3B-I) and Beclin 1 in T98G and U87MG cells. Further studies demonstrated that after pretreatment with 3-MA (3 mmol/L) for 48 h, siKDM4A-transfected cells showed a prominent decrease in LC3B-II/LC3B-I and Beclin 1, accompanied by increased viability and invasion and decreased apoptosis. Our results suggest that the inhibition of KDM4A expression might efficiently suppress glioma cell survival by promoting autophagy, providing a promising agent for treating malignant gliomas.

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Abbreviations

(KDM4A):

Lysine-specific demethylase 4A

(AVOs):

Acidic vesicular organelles

(AO):

Acridine orange

(3-MA):

3-Methyladenine

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Authors and Affiliations

  1. Department of Neurosurgery, Xi’an Central Hospital, Xi’an, 710003, China

    Bo Wang, Xinxin Fan, Qianfa Long & Yuan Chai

  2. Department of Neurosurgery, Xuzhou Central Hospital, No. 199 Liberation of South Road, Xuzhou City, Jiangsu, 221009, China

    Chong Ma

  3. Department of Neurology, Xi’an Central Hospital, Xi’an, 710003, China

    Hui Lei

Authors
  1. Bo Wang
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  2. Xinxin Fan
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  3. Chong Ma
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  4. Hui Lei
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  5. Qianfa Long
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  6. Yuan Chai
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Correspondence to Chong Ma.

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The authors declare that they have no conflicts of interest.

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Highlights

1. KDM4A could promote the progression of glioma in vitro.

2. KDM4A inhibited autophagy activity.

3. KDM4A promoted the progression of glioma cells by inhibiting autophagy.

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Wang, B., Fan, X., Ma, C. et al. Downregulation of KDM4A Suppresses the Survival of Glioma Cells by Promoting Autophagy. J Mol Neurosci 60, 137–144 (2016). https://doi.org/10.1007/s12031-016-0796-6

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  • DOI: https://doi.org/10.1007/s12031-016-0796-6

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