HDAC1 promotes the migration of human myeloma cells via regulation of the lncRNA/Slug axis

Int J Mol Med. 2022 Jan;49(1):3. doi: 10.3892/ijmm.2021.5058. Epub 2021 Nov 5.

Abstract

Understanding the mechanisms underlying malignancy in myeloma cells is important for targeted treatment and drug development. Histone deacetylases (HDACs) can regulate the progression of various cancer types; however, their roles in myeloma are not well known. In the present study, the expression of class I HDACs in myeloma cells and tissues was evaluated. Furthermore, the effects of HDAC1 on the migration of myeloma cells and the associated mechanisms were investigated. Among the class I HDACs evaluated, HDAC1 was upregulated in both myeloma cells and tissues. Targeted inhibition of HDAC1 suppressed the migration of myeloma cells. Of the assessed transcription factors, small interfering (si)‑HDAC1 decreased the expression of Slug. Overexpression of Slug reversed the si‑HDAC1‑mediated suppressed migration of myeloma cells. Mechanistically, the results revealed that HDAC1 regulated the mRNA stability of Slug, while it had no effect on its transcription or nuclear export. Furthermore, HDAC1 negatively regulated the expression of long non‑coding RNA (lncRNA) NONHSAT113026, which could bind with the 3'‑untranslated region of Slug mRNA to facilitate its degradation. The present study demonstrated that HDAC1 promoted the migration of human myeloma cells via regulation of lncRNA/Slug signaling.

Keywords: HDAC1; Slug; long non‑coding RNA; migration; myeloma.

MeSH terms

  • 3' Untranslated Regions
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Gene Expression Regulation, Neoplastic
  • Histone Deacetylase 1 / genetics*
  • Histone Deacetylase 1 / metabolism
  • Humans
  • Multiple Myeloma / genetics*
  • Multiple Myeloma / pathology*
  • RNA Stability
  • RNA, Long Noncoding / genetics*
  • Snail Family Transcription Factors / genetics*
  • Snail Family Transcription Factors / metabolism

Substances

  • 3' Untranslated Regions
  • RNA, Long Noncoding
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • HDAC1 protein, human
  • Histone Deacetylase 1

Grants and funding

The present study was supported by Fourth Pilot-Research Program for Human Space Flight (Grant/Award no. 020106).