Exosomal lncRNA HEIH promotes cisplatin resistance in tongue squamous cell carcinoma via targeting miR-3619-5p/HDGF axis

Acta Histochem. 2020 Dec;122(8):151647. doi: 10.1016/j.acthis.2020.151647. Epub 2020 Oct 30.

Abstract

Background: Accumulating evidence has suggested that long noncoding RNAs (lncRNAs) are involved in the progression of types of human cancers. It has been known that exosomes can mediate cell-cell crosstalk by transferring lncRNAs in tumor progression. This study aimed to investigate the role of exosomal lncRNA HEIH on cisplatin (DDP) resistance in tongue squamous cell carcinoma (TSCC).

Methods: The expression of HEIH in human oral keratinocytes cell line (HOK), DDP-sensitive TSCC cell line (SCC4/S) and DDP-resistant TSCC cell line (SCC4/DDP) was measured. SCC4/S and SCC4/DDP cells were transfected with sh-HEIH to examine TSCC cell proliferation and apoptosis. The DDP-resistant exosomes were extracted and identified. The expression of miR‑3619-5p and TDGF in DDP-sensitive recipient cells was determined. The binding capacity between HEIH and miR‑3619-5p, along with miR‑3619-5p and TDGF was verified.

Results: HEIH expression was significantly upregulated in SCC4/DDP cells. Downregulation of HEIH inhibited DDP resistance and cell proliferation and promoted cell apoptosis. HEIH acted as a competing endogenous RNA (ceRNA) for miR‑3619-5p to upregulate HDGF expression. Exosomal HEIH promoted cell proliferation and drug resistance and inhibited cell apoptosis by sponging miR‑3169-5p and upregulating HDGF.

Conclusion: Exosomal HEIH acted as a ceRNA for miR‑3619-5p to upregulate HDGF, thereby promoting DDP resistance in TSCC cells.

Keywords: Exosomes; HDGF; HEIH; TSCC; miR‑3619-5p.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / genetics
  • Base Pairing
  • Base Sequence
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm / genetics*
  • Epithelial Cells / metabolism*
  • Epithelial Cells / pathology
  • Exosomes / drug effects
  • Exosomes / genetics
  • Exosomes / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genes, Reporter
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Luciferases / genetics
  • Luciferases / metabolism
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Oligoribonucleotides / genetics
  • Oligoribonucleotides / metabolism
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • Signal Transduction

Substances

  • Antineoplastic Agents
  • Intercellular Signaling Peptides and Proteins
  • MIRN-3619 microRNA, human
  • MicroRNAs
  • Oligoribonucleotides
  • RNA, Long Noncoding
  • hepatoma-derived growth factor
  • Luciferases
  • Cisplatin