期刊
EUROPEAN JOURNAL OF CANCER
卷 48, 期 6, 页码 827-836出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2011.06.030
关键词
TAGLN2; MicroRNA; MiR-1; MiR-133a; Renal cell cancer
类别
资金
- Ministry of Education, Science, Sports and Culture [20390427, 20591861]
- Grants-in-Aid for Scientific Research [20591861, 20390427] Funding Source: KAKEN
Purpose: The aim of this study was to find a novel molecular network involved in renal cell carcinoma (RCC) development through investigating the functions of miR-1 and miR-133a and their target genes. Methods: We checked the expression levels of miR-1 and miR-133a in RCC cell lines and specimens (N = 40) using real time RT-PCR. MiR-1 and miR-133a transfectants were subjected to a gain-of-function study to identify the functions of the miRNAs. To find the target genes of the miRNAs, we analysed the gene expression profile of their transfectants and performed a luciferase reporter assay. mRNA expression levels of the candidate target gene in the clinical specimens were examined, and loss-of-function studies were performed. Results: The expression levels of miR-1 and miR-133a were significantly suppressed in RCC cell lines and specimens. Ectopic restoration of miR-1 and miR-133a showed significant inhibition of cell proliferation and invasion, and moreover, revealed induction of apoptosis and cell cycle arrest. The luciferase assay revealed transgelin-2 (TAGLN2), selected as a target gene for miR-1 and miR-133a on the basis of the gene expression profile, to be directly regulated by both miR-1 and miR-133a. The loss-of-function studies showed significant inhibitions of cell proliferation and invasion in the si-TAGLN2 transfectant. The expression level of TAGLN2 mRNA was significantly up-regulated in the RCC specimens; in addition, there was a statistically significant inverse correlation between TAGLN2 and miR-1 and miR-133a expression. Conclusions: Our data indicate that up-regulation of the oncogenic TAGLN2 was due to down-regulation of tumour-suppressive miR-1 and miR-133a in human RCC. (C) 2011 Elsevier Ltd. All rights reserved.
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