title: Cyclooxygenase-2, a Potential Therapeutic Target, Is Regulated by miR-101 in Esophageal Squamous Cell Carcinoma.
abstract: OBJECTIVE
  Cyclooxygenase-2 (COX-2) is known to promote the carcinogenesis of esophageal squamous cell carcinoma (ESCC). There are no reports on whether microRNAs (miRNAs) regulate COX-2 expression in ESCC. This study investigated the effect of miR-101 on ESCC through modulating COX-2 expression in ESCC.
  
  
  METHODS
  Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify miR-101 expression in ESCC clinical tissues and cell lines. The effects of miR-101 on ESCC progression were evaluated by cell counting kit-8 (CCK8), transwell migration and invasion assays, as well as by flow cytometry. The COX-2 and PEG2 levels were determined by western blot and enzyme-linked immunosorbent assays (ELISA). The luciferase reporter assay was used to verify COX-2 as a direct target of miR-101. The anti-tumor activity of miR-101 in vivo was investigated in a xenograft nude mouse model of ESCC.
  
  
  RESULTS
  Downregulation of miR-101 was confirmed through comparison of 30 pairs of ESCC tumor and adjacent normal tissues (P < 0.001), as well as in 11 ESCC cell lines and a human immortalized esophageal cell line (P < 0.001). Transfection of miR-101 in ESCC cell lines significantly suppressed cell proliferation, migration, and invasion (all P < 0.001). The antitumor effect of miR-101 was verified in a xenograft model. Furthermore, COX-2 was shown to be a target of miR-101.
  
  
  CONCLUSIONS
  Overexpression of miR-101 in ESCC inhibits proliferation and metastasis. Therefore, the miR-101/COX-2 pathway might be a therapeutic target in ESCC.
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
authors.forename: Sheng-tao
authors.initials: ST
authors.lastname: Zhu
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
authors.forename: Ji-ping
authors.initials: JP
authors.lastname: Yue
authors.affiliation: Intensive Care Unit, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Xiao-jun
authors.initials: XJ
authors.lastname: Ji
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Ma
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
authors.forename: Yong-jun
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zong
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
authors.forename: Yong-dong
authors.initials: YD
authors.lastname: Wu
authors.affiliation: Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Key Laboratory for Precancerous Lesion of Digestive Diseases, Beijing, China.
authors.forename: Shu-tian
authors.initials: ST
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation; D004790:Enzyme Induction / Q000235:genetics; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000628:therapy; D004947:Esophagus / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D017930:Genes, Reporter; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: C534072:MIRN101 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human