title: MiR-375 suppresses invasion and metastasis by direct targeting of SHOX2 in esophageal squamous cell carcinoma.
abstract: Esophageal squamous cell carcinoma (ESCC) is the most common histological type in China. MicroRNAs are endogenously expressed in mammals and play a significant role in tumor invasion and metastasis by targeting potential downstream genes. In the present study, microarray analysis showed that miR-375 expression was distinctly downregulated in ESCC compared with that in normal esophageal epithelium tissues. Then, luciferase reporter assay showed that SHOX2 was the direct downstream target of miR-375 and this interaction was confirmed by the rescue experiments. Quantitative polymerase chain reaction results also showed that SHOX2 expression was upregulated in ESCC cells and tissues. Further analysis showed that SHOX2 induced proliferation, invasion, and metastasis of ESCC both in vivo and in vitro. Moreover, the interaction between miR-375 and SHOX2 affected the epithelial-to-mesenchymal transition. We conclude that miR-375 may suppress invasion and metastasis of ESCC by directly targeting SHOX2. The miR-375/SHOX2 axis may be a novel therapeutic target for ESCC.
authors.affiliation: Department of Cardiothoracic Surgery, Jinling Hospital, Nanjing 210002, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yi
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Nanjing 210002, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Nanjing 210002, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Nanjing 210002, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Feng
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Nanjing 210002, China.
authors.forename: Zhenyue
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Nanjing 210002, China.
authors.forename: Longbang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Jinling Hospital, Nanjing 210002, China.
authors.forename: Haizhu
authors.initials: H
authors.lastname: Song
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous
chemical_list: D020413:3' Untranslated Regions; D018398:Homeodomain Proteins; C540933:MIRN375 microRNA, human; D035683:MicroRNAs; C484664:SHOX2 protein, human
keywords: SHOX2; esophageal squamous carcinoma cancer; invasion; metastasis; miR-375