2. Academic Validation
  3. HDAC1/2-mediated deacetylation of KLF9 promotes the malignant progression of nasopharyngeal carcinoma via CDH17

HDAC1/2-mediated deacetylation of KLF9 promotes the malignant progression of nasopharyngeal carcinoma via CDH17

  • Oncogene. 2025 Sep;44(35):3183-3198. doi: 10.1038/s41388-025-03471-4.
Kun Zhang 1,  Xingzhi Peng 1 2,  Peijun Zhou 1 2,  Xuanxuan Li 1,  Liangfang Shen 1,  Lifang Yang 3 4,  Qin Zhou 5
Affiliations

Affiliations

  • 1 Department of Oncology, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
  • 2 Cancer Research Institute, School of Basic Medicine Science, Central South University, Changsha, China.
  • 3 Department of Oncology, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. yanglifang@csu.edu.cn.
  • 4 Cancer Research Institute, School of Basic Medicine Science, Central South University, Changsha, China. yanglifang@csu.edu.cn.
  • 5 Department of Oncology, Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. zhouqin5796@csu.edu.cn.
PMID: 40615689 DOI: 10.1038/s41388-025-03471-4
Abstract

Protein acetylation modifications play an important role in the malignant progression and metastasis of tumors. The transcription factor KLF9 primarily functions as a transcriptional suppressor exerting Anticancer effects in some tumors. However, the expression regulation of KLF9 and its role in nasopharyngeal carcinoma (NPC) are not well understood. In the present study, we found that KLF9 exhibited deacetylation and low expression in NPC, and its overexpression inhibited the proliferation and metastasis of NPC. Mechanistically, the high expression of HDAC1/2 in tumor cells mediated the deacetylation of KLF9 at lysine 237/238, further inhibiting the K63 ubiquitination induced by the E3 ubiquitin Ligase SYVN1, thus reducing the protein stability and subsequent transcriptional inhibition function of KLF9. Meanwhile, we found that KLF9 could restrain the transcription and expression of cadherin-17 (CDH17), suppressing the malignant progression and metastasis of NPC. This research expands our comprehension of transcription factor expression regulation from the perspective of protein acetylation and ubiquitination interactions, providing novel molecular markers and therapeutic targets for NPC.

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