title: TNF-α is a novel target of miR-19a.
abstract: Many studies have demonstrated the overexpression and amplification of the miR-17-92 cluster in malignant human cancers, including B-cell lymphomas and lung cancers. The purpose of this study was to investigate for the first time, the expression of the miR-17-92 cluster in esophageal squamous cell carcinoma (ESCC). The miR-17-92 cluster was found to be overexpressed in 21 out of 28 (75%) esophageal cancer samples. It was also found that overexpression of the miR-17-92 cluster could promote cellular growth in vivo and in vitro. Furthermore, inhibition of miR-19a by antisense oligonucleotides (ONs) induced apoptosis, while antisense ONs against miR-17-5p, miR-18a, miR-20a and miR-92-1 did not exhibit such an effect. In addition, it was found that antagomir-19a treatment could impair tumor growth in vivo. Using Human Apoptosis RT2 Profiler PCR Array 384HT, we found that tumor necrosis factor-α (TNF-α) was up-regulated 12-fold in cells transfected with miR-19a antisense ONs compared to the cells treated with the control scramble ONs. MiR-19a was predicted to target the 3' untranslated region of TNF-α mRNA, and this was confirmed by luciferase reporter assay. Taken together, we conclude that the miR-17-92 cluster is overexpressed in ESCC and that TNF-α is a novel target of miR-19a.
authors.affiliation: Laboratory of Cell and Molecular Biology and State Key Laboratory of Molecular Oncology, Cancer Institute and Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Liu
authors.forename: Zaozao
authors.initials: Z
authors.lastname: Wang
authors.forename: Shangbin
authors.initials: S
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Shun
authors.initials: S
authors.lastname: He
authors.forename: Chenfei
authors.initials: C
authors.lastname: Hu
authors.forename: Hongxia
authors.initials: H
authors.lastname: Zhu
authors.forename: Lanping
authors.initials: L
authors.lastname: Quan
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Bai
authors.forename: Ningzhi
authors.initials: N
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009368:Neoplasm Transplantation; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D034622:RNA Interference; D014183:Transplantation, Heterologous; D047368:Tumor Burden; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C549214:MIRN19A microRNA, human; D035683:MicroRNAs; D016376:Oligonucleotides, Antisense; D014409:Tumor Necrosis Factor-alpha