RRC ID 66093
著者 Osako Y, Seki N, Koshizuka K, Okato A, Idichi T, Arai T, Omoto I, Sasaki K, Uchikado Y, Kita Y, Kurahara H, Maemura K, Natsugoe S.
タイトル Regulation of SPOCK1 by dual strands of pre-miR-150 inhibit cancer cell migration and invasion in esophageal squamous cell carcinoma.
ジャーナル J Hum Genet
Abstract Analysis of our microRNA (miRNA) expression signatures of human cancers based on RNA sequencing have shown that both strands of pre-miR-150, miR-150-5p (the guide strand) and miR-150-3p (the passenger strand), are significantly reduced in cancer tissues. We have investigated the functional significance of both strands of pre-miR-150 in cancer cells. The aim of this study was to investigate the antitumor function of these miRNAs and how these miRNAs regulated oncogenic targets in esophageal squamous cell carcinoma (ESCC). Ectopic expression studies demonstrated that both strands of pre-miR-150 miRNA inhibited ESCC cancer cell migration and invasion, indicating that both miR-150-5p and miR-150-3p acted as antitumor miRNAs. A combination of genome-wide gene expression analyses and in silico database searches showed that SPOCK1 (SPARC/osteonectin, cwcv and kazal-like domains proteoglycan 1) was a candidate target of miR-150-5p and miR-150-3p in ESCC cells. Luciferase reporter assays showed that SPOCK1 was directly regulated by these miRNAs. Silencing of SPOCK1 by small interfering RNA inhibited cancer cell migration and invasion. Overexpression of SPOCK1/SPOCK1 was confirmed by real-time PCR methods and immunohistochemistry. Taken together, downregulation of both strands of pre-miR-150 and overexpression of SPOCK1 are involved in ESCC pathogenesis. The involvement of passenger strand miRNAs in the regulation of cancer cell aggressiveness is a novel concept in RNA research.
巻・号 62(11)
ページ 935-944
公開日 2017-11-1
DOI 10.1038/jhg.2017.69
PII jhg201769
PMID 28659612
MeSH Carcinogenesis / genetics* Carcinoma, Squamous Cell / genetics* Carcinoma, Squamous Cell / pathology Cell Line, Tumor Cell Movement / genetics Cell Proliferation / genetics Esophageal Neoplasms / genetics* Esophageal Neoplasms / pathology Esophageal Squamous Cell Carcinoma Gene Expression Regulation, Neoplastic Humans MicroRNAs / genetics* Neoplasm Invasiveness / genetics Proteoglycans / genetics* Sequence Analysis, RNA
IF 2.831
リソース情報
ヒト・動物細胞 TE-1(RCB1894) TE-8(RCB2098)