Introduction
In developing countries, hypopharyngeal cancer is a common cancer, which
bring heavy economic burden to patients and their
families.1, 2 Because of the difficulty of early
diagnosis, the prognosis of hypopharyngeal cancer is
poor.3, 4 Now the use of human bone marrow mesenchymal
stem cells (hBMSCs) as a targeted vector for hypopharyngeal cancer gene
therapy is a new therapeutic approach.5 hBMSCs is a
kind of mesenchymal stem cell which have the ability of self-renewal and
differentiation, and can be induced to form adipocytes, osteoblasts,
chondrocytes, neural cells, pancreatic cells and other types of cells in
vitro.6, 7
Studies have shown that with the interaction of tumor inflammatory
factors hBMSCs can differentiate into cancer-associated fibroblasts
(CAFs), which is closely related to the tumor formation and
development.8 As an important component of tumor
stroma, CAFs can directly promote tumor growth. CAFs can induce
epithelial mesenchymal transformation (EMT) of cervical cancer
epithelial cells through IL-6/STAT3/Snail pathway in the tumor
microenvironment, thus promoting the invasion and metastasis of cervical
cancer.9 It remains unknown that what substances in
hypopharyngeal cancer tissue mediate the differentiation of hBMSCs into
CAF?
Tumor can contact and interact with other cells in the tumor
microenvironment by secreting exosomes. Taylor et
al.10 first proposed to diagnose ovarian cancer by
detecting miRNA in blood exocrines. It has been found that miRNAs from
tumor exosomes can mediate the information exchange between tumor cells
and the microenvironment of metastasis targets. MiRNAs are important
regulators of tumor cell proliferation and
apoptosis,11-13 and also play an important role in the
process of tumor cell invasion and metastasis.14-16
According to literature, abnormal increase of miRNA-21 expression level
has been detected in a variety of tumor specimens and cell lines,
including breast cancer, cervical cancer, lung cancer, pancreatic
cancer, prostate cancer, colorectal cancer and glioma. Therefore,
miRNA-21 is a universally recognized carcinogenic small
RNA.17 Although many literatures have reported that
the expression level of miRNA-21 in tumor cells is significantly
increased, the expression level of miRNA-21 in hypopharyngeal cancer and
its pathogenic role are still unclear.
Therefore, we propose the hypothesis that miR-21 plays an important role
in the proliferation and differentiation of hBMSCs through interacting
with hBMSCs in the tumor microenvironment.