1. HDAC4 mediated LHPP deacetylation enhances its destabilization and promotes the proliferation and metastasis of nasopharyngeal carcinoma.
- Author
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Sun X, Zhang K, Peng X, Zhou P, Qu C, Yang L, and Shen L
- Subjects
- Humans, Cell Line, Tumor, Cell Movement, Cell Proliferation, Gene Expression Regulation, Neoplastic, Histone Deacetylases genetics, Histone Deacetylases metabolism, Nasopharyngeal Carcinoma genetics, Nasopharyngeal Carcinoma metabolism, Repressor Proteins metabolism, Inorganic Pyrophosphatase metabolism, Nasopharyngeal Neoplasms pathology, Signal Transduction
- Abstract
Studies have shown that acetylation modification plays an important role in tumor proliferation and metastasis. Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is downregulated in certain tumors, as a tumor suppressor role. However, the regulation of LHPP expression and its function in nasopharyngeal carcinoma (NPC) remain unclear. In the present study, we found that LHPP was downregulated in NPC, and overexpression of LHPP inhibited the proliferation and invasion of NPC cells. Mechanistically, HDAC4 deacetylated LHPP at K6 and promoted the degradation of LHPP through TRIM21 mediated K48-linked ubiquitination. HDAC4 was confirmed to be highly expressed in NPC cells and promoted the proliferation and invasion of NPC cells through LHPP. Further research found that LHPP could inhibit the phosphorylation of tyrosine kinase TYK2, thereby inhibiting the activity of STAT1. In vivo, knockdown of HDAC4 or treatment with small molecule inhibitor Tasquinimod targeting HDAC4 could significantly inhibit the proliferation and metastasis of NPC by upregulating LHPP. In conclusion, our finding demonstrated that HDAC4/LHPP signal axis promotes the proliferation and metastasis of NPC through upregulating TYK2-STAT1 phosphorylation activation. This research will provide novel evidence and intervention targets for NPC metastasis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
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