LncRNA SNHG1 regulates the differentiation of Treg cells and affects the immune escape of breast cancer via regulating miR-448/IDO

Int J Biol Macromol. 2018 Oct 15;118(Pt A):24-30. doi: 10.1016/j.ijbiomac.2018.06.033. Epub 2018 Jun 8.

Abstract

Objective: To investigate the mechanism of lncRNA SNHG1 in the immune escape of breast cancer (BC).

Methods: SNHG1, miR-448 and IL-10 levels were evaluated by qRT-PCR. The protein levels of IDO and Foxp3 were measured by Western blot. SNHG1 and miR-448 interaction was tested by RIP assay and RNA pull-down assay. MiR-448 and IDO interaction was observed by luciferase reporter assay.

Results: Compared with CD4+T cells, miR-448 expression in CD4+ TIL cells was decreased, while the expression of SNHG1, IDO, IL-10 and Foxp3 were increased. Moreover, SNHG1 directly contacted with miR-448, which could negatively regulate IDO. In cells treated with siRNA-SNHG and miR-448 inhibitor, interference SNHG1 up-regulated miR-448 expression and down-regulated IDO expression, while miR-448 inhibitor reversed this effect. In addition, miR-448 inhibitor reversed the inhibitory effect of siRNA-SNHG1 on Treg cell differentiation, and siRNA-SNHG1 could reduce tumor volume and down-regulated the expressions of SNHG1, IL-10, IDO and Foxp3.

Conclusion: Interference SNHG1 could inhibit the differentiation of Treg cells by promoting miR-448 expression and reducing IDO level, thereby impeding the immune escape of BC.

Keywords: Breast cancer; IDO; SNHG1; Treg cell; miR-448.

MeSH terms

  • Breast Neoplasms / genetics*
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Differentiation / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology
  • MicroRNAs / genetics*
  • MicroRNAs / immunology
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / immunology
  • T-Lymphocytes, Regulatory / immunology
  • Xenograft Model Antitumor Assays

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • MIRN448 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • long non-coding RNA SNHG1, human