title: miR-1 suppresses the growth of esophageal squamous cell carcinoma in vivo and in vitro through the downregulation of MET, cyclin D1 and CDK4 expression.
abstract: Several aberrant microRNAs (miRNAs or miRs) have been implicated in esophageal cancer (EC), which is widely prevalent in China. However, their role in EC tumorigenesis has not yet been fully elucidated. In the present study, we determined that miR‑1 was downregulated in esophageal squamous cell carcinoma (ESCC) tissues compared with adjacent non-neoplastic tissues using RT-qPCR, and confirmed this using an ESCC cell line. Using a nude mouse xenograft model, we confirmed that the re-expression of miR‑1 significantly inhibited ESCC tumor growth. A tetrazolium assay and a trypan blue exclusion assay revealed that miR‑1 suppressed ESCC cell proliferation and increased apoptosis, whereas the silencing of miR‑1 promoted cell proliferation and decreased apoptosis, suggesting that miR‑1 is a novel tumor suppressor. To elucidate the molecular mechanisms of action of miR‑1 in ESCC, we investigated putative targets using bioinformatics tools. MET, cyclin D1 and cyclin-dependent kinase 4 (CDK4), which are involved in the hepatocyte growth factor (HGF)/MET signaling pathway, were found to be targets of miR‑1. miR‑1 expression inversely correlated with MET, cyclin D1 and CDK4 expression in ESCC cells. miR‑1 directly targeted MET, cyclin D1 and CDK4, suppressing ESCC cell growth. The newly identified miR‑1/MET/cyclin D1/CDK4 axis provides new insight into the molecular mechanisms of ESCC pathogenesis and indicates a novel strategy for the diagnosis and treatment of ESCC.
authors.affiliation: The 82nd Hospital of the People's Liberation Army, Huaian, Jiangsu 223001, P.R. China.
authors.forename: Sen
authors.initials: S
authors.lastname: Jiang
authors.affiliation: The 82nd Hospital of the People's Liberation Army, Huaian, Jiangsu 223001, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Gastroenterology, Shanghai Sixth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200030, P.R. China.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Yang
authors.affiliation: The 82nd Hospital of the People's Liberation Army, Huaian, Jiangsu 223001, P.R. China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Laboratory Medicine, Huaiyin Hospital of Huaian city, Huaian, Jiangsu 233004, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Pan
authors.affiliation: The 82nd Hospital of the People's Liberation Army, Huaian, Jiangsu 223001, P.R. China.
authors.forename: Haijin
authors.initials: H
authors.lastname: Huang
authors.affiliation: The 82nd Hospital of the People's Liberation Army, Huaian, Jiangsu 223001, P.R. China.
authors.forename: Xuyang
authors.initials: X
authors.lastname: Wen
authors.affiliation: The 82nd Hospital of the People's Liberation Army, Huaian, Jiangsu 223001, P.R. China.
authors.forename: Husheng
authors.initials: H
authors.lastname: Shan
authors.affiliation: The 82nd Hospital of the People's Liberation Army, Huaian, Jiangsu 223001, P.R. China.
authors.forename: Qianwen
authors.initials: Q
authors.lastname: Li
authors.affiliation: The 82nd Hospital of the People's Liberation Army, Huaian, Jiangsu 223001, P.R. China.
authors.forename: Yunxiang
authors.initials: Y
authors.lastname: Du
authors.affiliation: The 82nd Hospital of the People's Liberation Army, Huaian, Jiangsu 223001, P.R. China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D020413:3' Untranslated Regions; C530104:CCND1 protein, human; C544547:MIRN1 microRNA, human; D035683:MicroRNAs; D019938:Cyclin D1; D008156:Luciferases; D019859:Proto-Oncogene Proteins c-met; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4