title: Plasma miR-185 is decreased in patients with esophageal squamous cell carcinoma and might suppress tumor migration and invasion by targeting RAGE.
abstract: The receptor for advanced-glycation end products (RAGE) is upregulated in various cancers and has been associated with tumor progression, but little is known about its expression and regulation by microRNAs (miRNAs) in esophageal squamous cell carcinoma (ESCC). Here, we describe miR-185, which represses RAGE expression, and investigate the biological role of miR-185 in ESCC. In this study, we found that the high level of RAGE expression in 29 pairs of paraffin-embedded ESCC tissues was correlated positively with the depth of invasion by immunohistochemistry, suggesting that RAGE was involved in ESCC. We used bioinformatics searches and luciferase reporter assays to investigate the prediction that RAGE was regulated directly by miR-185. Besides, overexpression of miR-185 in ESCC cells was accompanied by 27% (TE-11) and 49% (Eca-109) reduced RAGE expression. The effect was further confirmed in RAGE protein by immunofluorescence in both cell lines. The effects were reversed following cotransfection with miR-185 and high-level expression of the RAGE vector. Furthermore, the biological role of miR-185 in ESCC cell lines was investigated using assays of cell viability, Ki-67 staining, and cell migration and invasion, as well as in a xenograft model. We found that overexpression of miR-185 inhibited migration and invasion by ESCC cells in vitro and reduced their capacity to develop distal pulmonary metastases in vivo partly through the RAGE/heat shock protein 27 pathway. Interestingly, in clinical specimens, the level of plasma miR-185 expression was decreased significantly (P = 0.002) in patients with ESCC [0.500; 95% confidence interval (CI) 0.248-1.676] compared with healthy controls (2.410; 95% CI 0.612-5.671). The value of the area under the receiver-operating characteristic curve was 0.73 (95% CI 0.604-0.855). In conclusion, our findings shed novel light on the role of miR-185/RAGE in ESCC metastasis, and plasma miR-185 has potential as a novel diagnostic biomarker in ESCC.
authors: Center of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China;
authors: Rongrong
authors: R
authors: Jing
authors: Center of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China;
authors: Wen
authors: W
authors: Chen
authors: Center of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China;
authors: Huimin
authors: H
authors: Wang
authors: Center of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China;
authors: Shaoqing
authors: S
authors: Ju
authors: Center of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China;
authors: Hui
authors: H
authors: Cong
authors: Department of Pediatrics, Affiliated Hospital of Nantong University, Nantong, China;
authors: Baolan
authors: B
authors: Sun
authors: Department of Pathology, Affiliated Hospital of Nantong University, Nantong, China.
authors: Qin
authors: Q
authors: Jin
authors: Center of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China;
authors: Shaopeng
authors: S
authors: Chu
authors: Center of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China;
authors: Lili
authors: L
authors: Xu
authors: Center of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, China; wscm163@163.com.
authors: Ming
authors: M
authors: Cui
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000097:blood* / Q000235:genetics / Q000556:secondary / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019295:Computational Biology; D030541:Databases, Genetic; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D018832:Molecular Chaperones; D009361:Neoplasm Invasiveness; D000067759:Receptor for Advanced Glycation End Products / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
chemical_list: C000593871:AGER protein, human; D014408:Biomarkers, Tumor; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; C552431:MIRN185 microRNA, human; D035683:MicroRNAs; D018832:Molecular Chaperones; D000067759:Receptor for Advanced Glycation End Products
keywords: esophageal squamous cell carcinoma; metastasis; microRNA-185; plasma; receptor for advanced-glycation end products