MicroRNA-21 promotes hypopharyngeal cancer induced transition of bone
marrow mesenchymal stem cells to cancer-associated fibroblasts
Abstract
Abstract Objective: At present, human bone marrow mesenchymal stem cells
(hBMSCs) used as target vectors for hypopharyngeal cancer is a new
therapeutic direction of great potential. However, hBMSCs would be
transmitted into cancer-associated fibroblasts(CAFs) under the induction
of hypopharyngeal cancer. Here, we aimed to determine whether
microRNA-21(miR-21) in exosomes from FaDu cells would play a role in
hypopharyngeal cancer induced transition of hBMSCs to CAFs. Methods:
qRT-PCR and western blot were employed to investigate expression level
of miR-21 in hypopharyngeal cancer patient samples and FaDu cells. The
exosomes were collected from FaDu cells then isolated and identified.
Cell morphological changes were observed by inverted phase contrast
microscope. Expression level of CAF-related proteins, includingα-SMA and
FAP, were assessed by qRT-PCR and western blot. Cell cycle of hBMSCs
were determined by flow cytometry. Results: MiR-21 expression level was
up-regulated in hypopharyngeal cancer tissue and FaDu cells. Exosomes
from FaDu cells promoted CAFs-like features of hBMSCs, including
up-regulation of α-SMA and FAP and cell morphological changes.
Proportions of hMBSCs in G1 phase significantly decreased, while
proportions of hMBSCs in G2 phase significantly decreased at the
presence of exosomes from FaDu cells. What’s more, miR-21 knock-out in
FaDu cells suppressed transition of bone marrow mesenchymal stem cells
to cancer-associated fibroblasts and reversed the cell cycle change.
Conclusions: Our data showed that miR-21 promotes hypopharyngeal cancer
induced transition of bone marrow mesenchymal stem cells to
cancer-associated fibroblasts. Keywords: Hypopharyngeal cancer, Bone
marrow mesenchymal stem cells, Cancer-associated fibroblasts,
MicroRNA-21, Exosomes