期刊
PATHOBIOLOGY
卷 82, 期 5, 页码 233-241出版社
KARGER
DOI: 10.1159/000438826
关键词
MicroRNAs; Colorectal cancer; miR-148a; Matrix metalloproteinase 7
资金
- Ministry of Education, Culture, Science, Sports and Technology of Japan
- Ministry of Health, Labor and Welfare of Japan
- National Institute of Biomedical Innovation (Program for Promotion of Fundamental Studies in Health Sciences)
- Japan Society for the Promotion of Science
- National Cancer Center Research and Development Fund [23-A-9]
Objective: Colorectal cancer (CRC) develops through the deregulation of gene expression and the accumulation of epigenetic abnormalities, leading to tumor cell acquisition of malignant features. MicroRNAs (miRNAs) play a critical role in cancer development, where they can act as oncogenes or oncosuppressors. Methods: miR-148a expression was measured by qRT-PCR in patients with colorectal adenoma (n = 21) and CRC (stage I-IV, n = 159) using formalin-fixed paraffin-embedded tissue samples. In situ hybridization (ISH) using an miR-148a-specific probe was also performed. To further confirm the direct effect of miR-148a on matrix metalloproteinase (MMP)7 expression in CRC, MTT and cell invasion assays using HT29 and WiDr cells were performed. Results: miR-148a expression was found to be clearly downregulated in high-grade adenoma compared to low-grade adenoma on both qRT-PCR and ISH analysis. Downregulation of miR-148a expression was significantly correlated with advanced clinicopathological features and was an independent prognostic classifier in patients with stage III CRC. In CRC cells and tissues, miR-148a expression was inversely correlated with the expression of MMP7. Conclusion: We showed the collaborative participation of miR-148a and MMP7 in CRC cell invasion. These results also demonstrate that the downregulation of miR-148a expression promotes CRC progression, especially carcinogenesis and cancer cell invasion. (C) 2015 S. Karger AG, Basel
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