SnoN/SKIL modulates proliferation through control of hsa-miR-720 transcription in esophageal cancer cells

Journal Article · Fri Jan 04 04:00:00 EST 2013 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2012.11.005· OSTI ID:22210361

Shinozuka, Eriko; Miyashita, Masao ^[1]; Mizuguchi, Yoshiaki ^[1]; Akagi, Ichiro ^[1]; Kikuchi, Kunio ^[2]; Makino, Hiroshi; Matsutani, Takeshi; Hagiwara, Nobutoshi; Nomura, Tsutomu; Uchida, Eiji ^[1]; Takizawa, Toshihiro ^[2]

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1. Department of Surgery for Organ Function and Biological Regulation, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo 113-8602 (Japan)
2. Department of Molecular Anatomy and Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-Ku, Tokyo 113-8602 (Japan)

Highlights: Black-Right-Pointing-Pointer SnoN modulated miR-720, miR-1274A, and miR-1274B expression levels in TE-1 cells. Black-Right-Pointing-Pointer miR-720 and miR-1274A suppressed the expression of target proteins p63 and ADAM9. Black-Right-Pointing-Pointer Silencing of SnoN significantly upregulated cell proliferation in TE-1 cells. Black-Right-Pointing-Pointer Esophageal cancer tissues have lower SnoN expression levels than normal tissues. Black-Right-Pointing-Pointer Esophageal cancer tissues have higher miR-720 expression levels than normal tissues. -- 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.

• OSTI ID: 22210361
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 430; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ALBUMINS
ANIMAL TISSUES
BLOOD SERUM
CARCINOMAS
CELL PROLIFERATION
ESOPHAGUS
TRANSCRIPTION