HDAC4 promotes nasopharyngeal carcinoma progression and serves as a therapeutic target

Histone deacetylases (HDACs) are involved in tumor progression, and some have been successfully targeted for cancer therapy. The expression of histone deacetylase 4 (HDAC4), a class IIa HDAC, was upregulated in our previous microarray screen. However, the role of HDAC4 dysregulation and mechanisms u...

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Bibliographic Details
Published in:Cell death & disease 2021-02, Vol.12 (2), p.137-137, Article 137
Main Authors: Cheng, Chun, Yang, Jun, Li, Si-Wei, Huang, Guofu, Li, Chenxi, Min, Wei-Ping, Sang, Yi
Format: Article
Language:English
Subjects:
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Antibodies
Biochemistry
Biomedical and Life Sciences
Cell Biology
Cell Culture
Cell cycle
Cell migration
Cell proliferation
DNA microarrays
E-cadherin
Histone deacetylase
Immunology
Life Sciences
Mesenchyme
Metastases
Metastasis
Nasopharyngeal carcinoma
Therapeutic applications
Throat cancer
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Summary:Histone deacetylases (HDACs) are involved in tumor progression, and some have been successfully targeted for cancer therapy. The expression of histone deacetylase 4 (HDAC4), a class IIa HDAC, was upregulated in our previous microarray screen. However, the role of HDAC4 dysregulation and mechanisms underlying tumor growth and metastasis in nasopharyngeal carcinoma (NPC) remain elusive. Here, we first confirmed that the HDAC4 levels in primary and metastatic NPC tissues were significantly increased compared with those in normal nasopharyngeal epithelial tissues and found that high HDAC4 expression predicted a poor overall survival (OS) and progression-free survival (PFS). Functionally, HDAC4 accelerated cell cycle G1/S transition and induced the epithelial-to-mesenchymal transition to promote NPC cell proliferation, migration, and invasion in vitro, as well as tumor growth and lung metastasis in vivo. Intriguingly, knockdown of N-CoR abolished the effects of HDAC4 on the invasion and migration abilities of NPC cells. Mechanistically, HDAC3/4 binds to the E-cadherin promoter to repress E-cadherin transcription. We also showed that the HDAC4 inhibitor tasquinimod suppresses tumor growth in NPC. Thus, HDAC4 may be a potential diagnostic marker and therapeutic target in patients with NPC.
ISSN:2041-4889
2041-4889
DOI:10.1038/s41419-021-03417-0