title: SnoN/SKIL modulates proliferation through control of hsa-miR-720 transcription in esophageal cancer cells.
abstract: It is now evident that changes in microRNA are involved in cancer progression, but the mechanisms of transcriptional regulation of miRNAs remain unknown. Ski-related novel gene (SnoN/SKIL), a transcription co-factor, acts as a potential key regulator within a complex network of p53 transcriptional repressors. SnoN has pro- and anti-oncogenic functions in the regulation of cell proliferation, senescence, apoptosis, and differentiation. We characterized the roles of SnoN in miRNA transcriptional regulation and its effects on cell proliferation using esophageal squamous cell carcinoma (ESCC) cells. Silencing of SnoN altered a set of miRNA expression profiles in TE-1cells, and the expression levels of miR-720, miR-1274A, and miR-1274B were modulated by SnoN. The expression of these miRNAs resulted in changes to the target protein p63 and a disintegrin and metalloproteinase domain 9 (ADAM9). Furthermore, silencing of SnoN significantly upregulated cell proliferation in TE-1 cells, indicating a potential anti-oncogenic function. These results support our observation that cancer tissues have lower expression levels of SnoN, miR-720, and miR-1274A compared to adjacent normal tissues from ESCC patients. These data demonstrate a novel mechanism of miRNA regulation, leading to changes in cell proliferation.
authors.affiliation: Department of Surgery for Organ Function and Biological Regulation, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo 113-8602, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Shinozuka
authors.forename: Masao
authors.initials: M
authors.lastname: Miyashita
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Mizuguchi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Akagi
authors.forename: Kunio
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Makino
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsutani
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Hagiwara
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nomura
authors.forename: Eiji
authors.initials: E
authors.lastname: Uchida
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Takizawa
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C568636:MIRN720 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; C060615:SKIL protein, human