Abstract
CD47 inhibits phagocytosis and its overexpression is correlated with poor prognosis in patients with several types of cancer. It has also been reported that CD47 expression in multiple sclerosis is regulated by microRNAs. However, the regulatory mechanism of CD47 in cancer tissues has not been yet clarified. Re-analysis of a public microarray database revealed that miR-133a is downregulated in esophageal squamous cell carcinoma (ESCC). Moreover, insilico algorithms predicted that miR-133a is a regulator of CD47. The purpose of this study was to clarify the clinical significance of CD47 and its regulatory mechanism by miR-133a in ESCC. Quantitative real-time RT-PCR was used to evaluate CD47 and miR-133a expression in 102 cases of curative resected ESCC and adjacent non-cancerous tissue. The regulation of CD47 by miR-133a was examined with precursor miR-133a-transfected cells. A mouse xenograft model was used to investigate the ability of miR-133a to suppress tumor progression. High expression levels of CD47 were associated with lymph node metastasis (P=0.049). Multivariate analysis showed that CD47 expression was an independent prognostic factor (P=0.045). miR-133a expression was significantly lower in cancer tissues compared to adjacent non-cancerous tissues (P<0.001). Invitro assays showed that miR-133a is a direct regulator of CD47. miR‑133a significantly inhibited tumorigenesis and growth invivo. CD47 expression is a novel prognostic marker in ESCC that is directly inhibited by the miR-133a tumor suppressor. This correlation could provide new insight into the mechanism of cancer progression and a promising candidate for target therapy in ESCC.
Highlights
Esophageal squamous cell carcinoma (ESCC) has one of the highest mortality rates among patients with solid tumors due to the fact that it is a highly aggressive malignancy with early lymphatic and hematogenous dissemination [1,2]
Because tumor suppressive miRNAs are usually underexpressed in tumors, it has been suggested that miR-133a functions as a tumor suppressor
This study revealed that miR-133a inhibited tumor growth in an ESCC xenograft mouse model
Summary
Esophageal squamous cell carcinoma (ESCC) has one of the highest mortality rates among patients with solid tumors due to the fact that it is a highly aggressive malignancy with early lymphatic and hematogenous dissemination [1,2]. CD47 is a widely expressed transmembrane protein that has been implicated in multiple cellular processes, including a function as a ‘do not eat me’ signal inhibiting macrophage activity by binding the signal regulatory protein α, which is expressed on phagocytes [6,7,8]. Whereas this function is partly attributed to ‘self recognition’ in normal physiological conditions, several human cancers appear to upregulate CD47 to evade the tumor immunosurveillance system [9,10,11]. The clinicopathological and prognostic significance of CD47 expression in ESCC remains unclear
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