Effect of tumor exosome-derived Lnc RNA HOTAIR on the growth and metastasis of gastric cancer

Clin Transl Oncol. 2023 Dec;25(12):3447-3459. doi: 10.1007/s12094-023-03208-3. Epub 2023 May 18.

Abstract

Purpose: HOX transcribed antisense RNA (HOTAIR) is a long noncoding RNA (LncRNA) that promotes tumor progression. Exosomes are critically involved in cancer progression. The presence of HOTAIR in the circulating exosomes and the roles of exosomal HOTAIR in gastric cancer (GC) remains unknown. This study aimed to investigate the role of HOTAIR in exosomes in promoting the growth and metastasis of GC.

Methods: Serum exosomes from GC patients were captured by CD63 immunoliposome magnetic spheres (CD63-IMS), and the biological characteristics of the exosomes were identified. The expression levels of HOTAIR in GC cells, tissues, serum and serum exosomes were detected by fluorescence quantitative PCR (qRT-PCR), and the clinicopathological correlation was statistically analyzed. The growth and metastasis abilities of GC cells with HOTAIR knockdown in vitro were evaluated by cell experiment. The effects of HOTAIR highly-expressed NCI-N87 cell-derived exosomes were used to treat HOTAIR lowly-expressed MKN45 cells on GC growth and metastasis were also evaluated.

Results: The exosomes isolated by CD63-IMS had a particle size of 89.78 ± 4.8 nm and were oval membranous particles. The expression of HOTAIR in tumor tissues and serum of GC patients was increased (P < 0.05), and the expression of HOTAIR in serum exosomes was significantly increased (P < 0.01). The in NCI-N87 and MKN45 cell experiment demonstrated that HOTAIR knockdown by RNA interference suppressed cell growth and metastasis in NCI-N87 cells. Coculture of exosomes secreted by NCI-N87 cells with MKN45 cells significantly increased the expression of HOTAIR, and enhanced cell growth and metastasis.

Conclusion: LncRNA HOTAIR can be used as a potential biomarker which provides a new way for the diagnosis and treatment of GC.

Keywords: Biomarkers; Exosomes; Gastric cancer; HOTAIR; Immunolipid magnetic spheres.

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Exosomes* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Humans
  • RNA, Antisense
  • RNA, Long Noncoding* / metabolism
  • Stomach Neoplasms* / pathology

Substances

  • Biomarkers, Tumor
  • RNA, Antisense
  • RNA, Long Noncoding
  • HOTAIR long untranslated RNA, human