https://scholars.lib.ntu.edu.tw/handle/123456789/462222
標題: | Connective tissue growth factor modulates oral squamous cell carcinoma invasion by activating a miR-504/FOXP1 signalling | 作者: | Yang M.-H. BEEN-REN LIN CHIA-HSUIN CHANG Chen S.-T. SZE-KWAN LIN YEN-PING KUO YUNG-MING JENG Kuo M.-L. Chang C.-C. |
公開日期: | 2012 | 出版社: | Nature Publishing Group | 卷: | 31 | 期: | 19 | 起(迄)頁: | 2401-2411 | 來源出版物: | Oncogene | 摘要: | Connective tissue growth factor (CTGF) is a multi-functional secreted protein, and it has been shown either to promote or suppress tumor progression among different kinds of cancers. Here, we investigated the role of CTGF in oral squamous cell carcinoma (OSCC) invasion and metastasis. In five OSCC cell lines, endogenous CTGF negatively correlated with invasiveness. Exogenous CTGF protein or forced expression of CTGF gene in the oral cancer cell line SAS significantly decreased their invasive and migratory abilities. MicroRNA (miRNA) microarray analysis was performed in CTGF-overexpressed SAS cells (SAS/CTGF-M3) versus control cells to investigate the mechanism of CTGF-mediated inhibition of OSCC invasion. Among the miRNAs regulated by CTGF, miR-504 and miR-346 were the top two miRNAs downregulated in CTGF transfectants, and the result was confirmed by quantitative reverse transcriptase-PCR. Ectopic miR-504 increased migration and invasion in SAS/CTGF-M3, however, miR-346 did not have such impact on migration/invasion. Furthermore, we identified FOXP1, a member of forkhead transcription factors, as a target gene that takes part in the miR-504-induced cellular invasion. Knockdown of FOXP1 increased invasiveness in SAS/CTGF-M3, confirming the signal axis of CTGF/miR-504/FOXP1 in OSCC. Animal experiments showed that SAS/CTGF-M3-formed orthotopic tumors were associated with a lesser invasive phenotype than control cells. Expression of miR-504 in SAS/CTGF-M3 increased lymph node metastasis, and co-expression of FOXP1 in miR-504-transfected SAS/CTGF-M3 alleviated miR-504-induced metastasis. In OSCC samples, high CTGF was associated with a lower clinical stage and a better outcome. A reverse correlation between CTGF and miR-504, miR-504 and FOXP1, and a positive correlation between CTGF and FOXP1 were shown. Our study discovers a novel signal pathway involving the regulation of miRNA machinery by a secreted cytokine, which will be beneficial for developing therapeutic strategy against advanced OSCC. ? 2012 Macmillan Publishers Limited All rights reserved. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84861348585&doi=10.1038%2fonc.2011.423&partnerID=40&md5=b72cfb58d6b39643697b91853c602b94 https://scholars.lib.ntu.edu.tw/handle/123456789/462222 |
ISSN: | 0950-9232 | DOI: | 10.1038/onc.2011.423 | SDG/關鍵字: | connective tissue growth factor; microRNA; microRNA 504; transcription factor; transcription factor FOXP1; unclassified drug; animal experiment; animal model; article; cancer cell culture; cancer invasion; cell invasion; cell migration; controlled study; correlation analysis; female; gene expression; gene silencing; human; human cell; human tissue; lymph node metastasis; microarray analysis; mouse; mouth squamous cell carcinoma; nonhuman; phenotype; priority journal; protein analysis; protein expression; reverse transcription polymerase chain reaction; RNA analysis; signal transduction; Animalia |
顯示於: | 醫學系 |
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