Loss of exosomal miR-34c-5p in cancer-associated fibroblast for the maintenance of stem-like phenotypes of laryngeal cancer cells.

Abstract

Cancer-associated fibroblasts (CAFs) reconstitute cancer stemness. This study aims to investigate whether the loss of CAF-derived exosomal miR-34c-5p contributes to the maintenance of stem-like properties of laryngeal squamous cell carcinoma (LSCC). Exosomes from primarily cultured CAFs and paired normal fibroblasts (NFs) were collected and identified. The differential expression of exosomal miR-34c-5p between CAFs and NFs was detected by next-generation sequencing. In vitro and in vivo assays were performed to examine the effects of miR-34c-5p on the maintenance of stem-like properties. MiR-34c-5p expression is significantly reduced in CAF-derived exosomes. In vitro and in vivo assays revealed that exosomal miR-34c-5p can regulate the stem-like properties of LSCC cells, such as proliferation, invasion, sphere and plate colony formation, chemoresistance, tumorigenicity in nude mice, as well as the expression of cancer stem cell genes. Loss of miR-34c-5p in CAF-derived exosomes contributes to the maintenance of stem-like phenotypes of LSCC.