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.