RRC ID 64902
著者 Osako Y, Seki N, Kita Y, Yonemori K, Koshizuka K, Kurozumi A, Omoto I, Sasaki K, Uchikado Y, Kurahara H, Maemura K, Natsugoe S.
タイトル Regulation of MMP13 by antitumor microRNA-375 markedly inhibits cancer cell migration and invasion in esophageal squamous cell carcinoma.
ジャーナル Int J Oncol
Abstract Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive malignancies. Recently developed molecular targeted therapies are not available for patients with ESCC. After curative surgical resection, patients frequently suffer distant metastasis and recurrence. Exploration of novel ESCC metastatic pathways may lead to the development of new treatment protocols for this disease. Accordingly, we have sequentially identified microRNA (miRNA)-mediated metastatic pathways in several cancers. Our past studies of miRNA expression signatures have shown that microRNA-375 (miR-375) is frequently reduced in several types of cancers, including ESCC. In the present study, we aimed to investigate novel miR-375-mediated metastatic pathways in ESCC cells. The expression of miR-375 was downregulated in ESCC tissues, and ectopic expression of this miRNA markedly inhibited cancer cell migration and invasion, suggesting that miR-375 acted as an antimetastatic miRNA in ESCC cells. Our strategies for miRNA target searching demonstrated that matrix metalloproteinase 13 (MMP13) was directly regulated by miR-375 in ESCC cells. Overexpression of MMP13 was observed in ESCC clinical tissues, and the expression of MMP13 promoted cancer cell aggressiveness. Moreover, oncogenic genes, including CENPF, KIF14 and TOP2A, were shown to be regulated downstream of MMP13. Taken together, these findings demonstrated that the antitumor miR-375/oncogenic MMP13 axis had a pivotal role in ESCC aggressiveness. These results provide novel insights into the potential mechanisms of ESCC pathogenesis.
巻・号 49(6)
ページ 2255-2264
公開日 2016-12-1
DOI 10.3892/ijo.2016.3745
PMID 27779648
PMC PMC5117997
MeSH Aged Aged, 80 and over Antigens, Neoplasm / genetics Carcinoma, Squamous Cell / genetics Carcinoma, Squamous Cell / pathology* Cell Line, Tumor Cell Movement / genetics* Cell Proliferation / genetics Chromosomal Proteins, Non-Histone / genetics DNA Topoisomerases, Type II / genetics DNA-Binding Proteins / genetics Esophageal Neoplasms / genetics Esophageal Neoplasms / pathology* Esophageal Squamous Cell Carcinoma Female Gene Expression Regulation, Neoplastic Humans Kinesins / genetics Male Matrix Metalloproteinase 13 / genetics* MicroRNAs / genetics* Microfilament Proteins / genetics Middle Aged Neoplasm Invasiveness / genetics Neoplasm Recurrence, Local / genetics Oncogene Proteins / genetics Poly-ADP-Ribose Binding Proteins RNA Interference RNA, Small Interfering / genetics
IF 4.087
リソース情報
ヒト・動物細胞 TE-8(RCB2098) TE-9(RCB1988)