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 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, in silico 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).             In vitro assays showed that miR-133a is a direct regulator of CD47. miR‑133a significantly             inhibited tumorigenesis and growth in vivo. 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.
Department of General Surgical Science, Gunma University, Graduate School of Medicine, Gunma 371-8511, Japan. suzukis@med.gunma-u.ac.jp
Shigemasa
S
Suzuki
Takehiko
T
Yokobori
Naritaka
N
Tanaka
Makoto
M
Sakai
Akihiko
A
Sano
Takanori
T
Inose
Makoto
M
Sohda
Masanobu
M
Nakajima
Tatsuya
T
Miyazaki
Hiroyuki
H
Kato
Hiroyuki
H
Kuwano
D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D051928:CD47 Antigen / Q000096:biosynthesis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D020869:Gene Expression Profiling; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011379:Prognosis; D014162:Transfection; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays
D014408:Biomarkers, Tumor; D051928:CD47 Antigen; C497894:CD47 protein, human; C548234:MIRN133 microRNA, human; D035683:MicroRNAs