Aerosolized miR-138-5p and miR-200c targets PD-L1 for lung cancer prevention

Qi Zhang, Jing Pan, Donghai Xiong, Junjun Zheng, Kristi N. McPherson, Sangbeom Lee, Mofei Huang, Yitian Xu, Shu Hsia Chen, Yian Wang, Lea Hildebrandt Ruiz, Ming You

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

The development of chemopreventive strategies with the ability to prevent the progression of lung lesions to malignant cancers would reduce the mortality and morbidity resulting from this deadly disease. Delivery of microRNA (miRNA) by inhalation is a novel method for lung cancer prevention. In this study, we investigated the combined efficacy of aerosolized miR-138-5p and miR-200c miRNA mimics in lung cancer prevention. Combination of the two miRNAs inhibited Benzo(a)pyrene (B((a))P)-induced lung adenomas and N-nitroso-tris-chloroethylurea (NTCU)-induced lung squamous cell carcinomas with no detectable side effects. Using single-cell RNA sequencing (scRNA-seq) and imaging mass cytometry (IMC), we found that both miRNAs inhibited programmed cell death ligand 1 (PD-L1) expression. Our flow cytometry results showed that aerosolized delivery of combined miRNAs increased CD4+ and CD8+ T cells and reduced the expression of programmed cell death protein 1 (PD-1) and T-regulatory cells. Our results demonstrated that the delivery of aerosolized microRNAs targeting PD-L1 can be highly effective in preventing lung cancer development and progression in mice.

Original languageEnglish
Article number1166951
JournalFrontiers in Immunology
Volume14
DOIs
StatePublished - 2023
Externally publishedYes

Keywords

  • MiR-200c
  • MicroRNAs
  • aerosol delivery
  • lung carcinogenesis
  • miR-138-5p
  • tumor immune microenvironment

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