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Molecular Profiling of the Invasive Tumor Microenvironment in a 3-Dimensional Model of Colorectal Cancer Cells and Ex vivo Fibroblasts
Published on: April 29, 2014
A MicroRNA expression profile defining the invasive bladder tumor phenotype
Matthew F Wszolek1, Kimberly M Rieger-Christ, Patrick A Kenney
1Department of Urology, Lahey Clinic Medical Center, Burlington, MA 01805, USA.
Urologic Oncology
|December 1, 2009
Summary
Researchers identified specific microRNAs (miRNAs) that play a role in bladder cancer progression. A panel of three miRNAs shows high accuracy in detecting invasive urothelial carcinoma of the bladder (UCB).
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Urothelial carcinoma of the bladder (UCB) is a significant health concern.
- Understanding the molecular mechanisms driving the transition from noninvasive to invasive UCB is crucial for improved diagnostics and treatment.
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and are implicated in various cancers.
Purpose of the Study:
- To identify specific microRNAs (miRNAs) involved in the phenotypic switch from noninvasive to invasive urothelial carcinoma of the bladder (UCB).
- To assess the potential of identified miRNAs as diagnostic biomarkers for invasive UCB.
Main Methods:
- Differential miRNA expression analysis using microarrays in noninvasive and invasive UCB cell lines.
- Validation of miRNA expression using quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) in cell lines and 57 UCB tumor samples.
- Functional assessment of miRNA roles in invasion by transfecting pre-miR constructs into UCB cell lines.
Main Results:
- Microarray analysis revealed differential expression of several miRNAs, with reduced levels of miR-30b, miR-31, miR-141, miR-200a, miR-200b, miR-200c, miR-205, and miR-21 in invasive UCB lesions.
- Elevated miR-99a expression was observed in noninvasive UCB lesions.
- Transfection with pre-miRNAs, except for miR-30b, reduced the invasive potential of UCB cell lines, confirming their role in the invasive phenotype.
Conclusions:
- A panel of three miRNAs (miR-200c, miR-141, and miR-30b) demonstrated high diagnostic accuracy (100% sensitivity, 96.2% specificity) for identifying invasive UCB.
- This miRNA panel has the potential to improve the pathological assessment of bladder biopsy specimens and identify misclassified invasive tumors.
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