Exosomal lncRNA HOTAIR induce macrophages to M2 polarization via PI3K/ p-AKT /AKT pathway and promote EMT and metastasis in laryngeal squamous cell carcinoma

BMC Cancer. 2022 Nov 24;22(1):1208. doi: 10.1186/s12885-022-10210-5.

Abstract

Exosomes are a new way of the communication between the tumor cell and macrophage in the micro-environment. The macrophage can be induced to different phenotypes according to the different tumors. In the present study, long-chain noncoding RNA HOTAIR (lncRNA HOTAIR) was highly expressed in LSCC and exosomes. The pathway of exosomal lncRNA HOTAIR inducing macrophage to M2 polarization in the LSCC was investigated. The carcinoma tissues and adjacent tissues were collected from 104 LSCC cases, and the positive relationship between CD163-/CD206-M2 macrophage infiltration and clinical phase, lymph node spreading and pathological phase in LSCC was observed. To examine the role of exosomal lncRNA HOTAIR, macrophages were co-cultured with LSCC-exosomes of high lncRNA HOTAIR expression or transferred with HOTAIR mimics. It was suggested that exosomal lncRNA HOTAIR can induce macrophages to M2 polarization by PI3K/p-AKT/AKT signaling pathway. Furthermore, exo-treated M2 macrophages facilitate the migration, proliferation, and EMT of LSCC.

Keywords: EMT; Exosomes; LSCC; Macrophage; lncRNA HOTAIR.

MeSH terms

  • Cell Proliferation / genetics
  • Epithelial-Mesenchymal Transition*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Laryngeal Neoplasms* / genetics
  • Laryngeal Neoplasms* / pathology
  • Macrophages / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Long Noncoding* / genetics
  • Squamous Cell Carcinoma of Head and Neck* / genetics
  • Squamous Cell Carcinoma of Head and Neck* / pathology
  • Tumor Microenvironment / genetics

Substances

  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • RNA, Long Noncoding
  • HOTAIR long untranslated RNA, human