CD47 expression regulated by the miR-133a tumor suppressor is a novel prognostic marker in esophageal squamous cell carcinoma

CD47 inhibits phagocytosis and its overexpression is correlated with poorprognosis in patients with several types of cancer. It has also been reportedthat 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 downregulatedin esophageal squamous cell carcinoma (ESCC). Moreover, in silico algorithms predictedthat miR-133a is a regulator of CD47. The purpose of this study was to clarifythe clinical significance of CD47 and its regulatory mechanism by miR-133a inESCC. Quantitative real-time RT-PCR was used to evaluate CD47 and miR-133a expressionin 102 cases of curative resected ESCC and adjacent non-cancerous tissue. Theregulation of CD47 by miR-133a was examined with precursor miR-133a-transfectedcells. A mouse xenograft model was used to investigate the ability of miR-133ato suppress tumor progression. High expression levels of CD47 were associatedwith lymph node metastasis (P=0.049). Multivariate analysis showed that CD47 expressionwas an independent prognostic factor (P=0.045). miR-133a expression was significantlylower in cancer tissues compared to adjacent non-cancerous tissues (P<0.001).In vitro assays showed that miR-133a is a direct regulator of CD47. miR‑133a significantlyinhibited tumorigenesis and growth in vivo. CD47 expression is a novel prognosticmarker in ESCC that is directly inhibited by the miR-133a tumor suppressor. Thiscorrelation could provide new insight into the mechanism of cancer progressionand a promising candidate for target therapy in ESCC.