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HDAC2-mediated upregulation of IL-6 triggers the migration of osteosarcoma cells

  • Jing Li
  • Xiuzhong Yan
  • Jiaxing Tang
  • Yan Wang
  • Jian Tang
  • Wen WuEmail author
  • Ming LiuEmail author
Original Article
  • 20 Downloads

Abstract

Understanding the mechanisms of advanced metastasis in osteosarcoma (OS) cell is important for the targeted treatment and drug development. Emerging evidence shows that epigenetic factors such as histone deacetylases (HDACs) are involved in the progression and chemoresistance of OS, while their roles are largely unknown. Our data showed that the expression of HDAC2, while not HDAC1, 4, or 8, was significantly increased in OS cells and tissues. OS patients with increased expression of HDAC2 showed reduced overall survival with p value of 0.0001. Targeted inhibition of HDAC2 suppressed the in vitro migration and invasion of OS cells. Our data showed that the inhibition of HDAC2 can decrease the expression and transcription of interleukin-6 (IL-6) in OS cells. Overexpression of IL-6 can reverse si-HDAC2-induced suppression of cell migration. Mechanistical studies showed that inhibition of HDAC2 decreased the phosphorylation and nuclear accumulation of p65, the key factor of NF-κB complex responsible for the transcription of IL-6. This was due to that HDAC2 can activate the transcription of IKK-β in OS cells. Collectively, our data showed that HDAC2-activated NF-κB can increase the expression of IL-6 in OS cells, which resulted in the promotion of cell migration. It suggested that targeted inhibition of HDAC2/NF-κB/IL-6 might be a potential approach for OS therapy.

Keywords

HDAC2 IL-6 Osteosarcoma p65 IKK-β 

Notes

Funding information

This research was supported by the National Natural Science Foundation of China (Grant No. 81301546).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Orthopedic DepartmentTCM Hospital of RizhaoRizhaoChina
  2. 2.Orthopedic Department, Shanghai Ninth People’s Hospital, School of MedicineShanghai Jiaotong UniversityShanghaiChina

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