HDAC1 regulates the chemosensitivity of laryngeal carcinoma cells via modulation of interleukin-8 expression
Autor: | Ruoting Tang, Yongjun Jiang, Bohua Qing, Yanhong Wei, Zhaohui Tang, Sijuan Ding, Pengfei Luo, Siyuan Zhang |
---|---|
Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
animal structures Antineoplastic Agents Histone Deacetylase 1 03 medical and health sciences 0302 clinical medicine Transcription (biology) Cell Line Tumor Carcinoma medicine Humans Interleukin 8 3' Untranslated Regions Laryngeal Neoplasms Cell Proliferation Pharmacology Cisplatin Messenger RNA Gene knockdown Chemistry Squamous Cell Carcinoma of Head and Neck Interleukin-8 medicine.disease Head and neck squamous-cell carcinoma HDAC1 Gene Expression Regulation Neoplastic enzymes and coenzymes (carbohydrates) 030104 developmental biology Drug Resistance Neoplasm embryonic structures Cancer research Fluorouracil biological phenomena cell phenomena and immunity 030217 neurology & neurosurgery medicine.drug Signal Transduction |
Zdroj: | European journal of pharmacology. 896 |
ISSN: | 1879-0712 |
Popis: | Chemotherapies such as 5-fluorouracil (5-FU) and cisplatin (CDDP) have been widely used to treat laryngeal squamous cell carcinoma (LSCC), the second most common head and neck squamous cell carcinoma. However, chemoresistance seriously impairs chemotherapeutic efficacy. Our present study reveals that 5-FU and CDDP treatment increase the expression of histone deacetylase 1 (HDAC1) in LSCC cells. Consistently, increased levels of HDAC1 are observed in chemoresistant cells. Knockdown of HDAC1 significantly restores the sensitivity of LSCC cells, as HDAC1 increases the expression of interleukin-8 (IL-8), which is essential for LSCC chemoresistance. Mechanistically, HDAC1 directly initiates the transcription of IL-8 though binding to its promoter. Simultaneously, si-HDAC1 increases the levels of miR-93, which binds to the 3'UTR of IL-8 mRNA to trigger its degradation. In summary, the HDAC1/IL-8 axis can confer chemotherapeutic resistance to LSCC cells. |
Databáze: | OpenAIRE |
Externí odkaz: |