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miRNA Profiling in Colorectal Cancer Highlights miR-1 Involvement in MET-Dependent Proliferation
- Source :
- Molecular Cancer Research, 10(4), 504-515
- Publication Year :
- 2012
- Publisher :
- American Association for Cancer Research (AACR), 2012.
-
Abstract
- Altered expression of miRNAs is associated with development and progression of various human cancers by regulating the translation of oncogenes and tumor suppressor genes. In colorectal cancer, these regulators complement the Vogelstein multistep model of pathogenesis and have the potential of becoming a novel class of tumor biomarkers and therapeutic targets. Using quantitative real-time PCR, we measured the expression of 621 mature miRNAs in 40 colorectal cancers and their paired normal tissues and identified 23 significantly deregulated miRNAs. We subsequently evaluated their association with clinical characteristics of the samples and presence of alterations in the molecular markers of colorectal cancer progression. Expression levels of miR-31 were correlated with CA19-9 and miR-18a, miR-21, and miR-31 were associated with mutations in APC gene. To investigate the downstream regulation of the differentially expressed miRNAs identified, we integrated putative mRNA target predictions with the results of a meta-analysis of seven public gene expression datasets of normal and tumor samples of colorectal cancer patients. Many of the colorectal cancer deregulated miRNAs computationally mapped to targets involved in pathways related to progression. Here one promising candidate pair (miR-1 and MET) was studied and functionally validated. We show that miR-1 can have a tumor suppressor function in colorectal cancer by directly downregulating MET oncogene both at RNA and protein level and that reexpression of miR-1 leads to MET-driven reduction of cell proliferation and motility, identifying the miR-1 downmodulation as one of the events that could enhance colorectal cancer progression. Mol Cancer Res; 10(4); 504–15. ©2012 AACR.
- Subjects :
- Cancer Research
Colorectal cancer
Down-Regulation
Cell Growth Processes
Mouse model of colorectal and intestinal cancer
Biology
Transfection
law.invention
Cohort Studies
Downregulation and upregulation
Cell Movement
law
Cell Line, Tumor
Gene expression
microRNA
medicine
Humans
Molecular Biology
Gene
Cell Proliferation
Regulation of gene expression
Gene Expression Profiling
Proto-Oncogene Proteins c-met
medicine.disease
Gene Expression Regulation, Neoplastic
MicroRNAs
Oncology
Cancer research
Suppressor
Colorectal Neoplasms
Subjects
Details
- ISSN :
- 15573125 and 15417786
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- Molecular Cancer Research
- Accession number :
- edsair.doi.dedup.....4a6859293a530904cb79413cff26f66f