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DICER1 and PRKRA in Colon Adenocarcinoma
S Chiosea1, M Acquafondata, J Luo
1Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA, U.S.A.
Abstract:
Differential microRNA expression in colon adenocarcinoma (CA) was previously reported. MicroRNA biogenesis and function requires a set of proteins designated as the microRNA machinery, which includes DICER1 and PRKRA. Loss of heterozygosity at 14q32.13 DICER1 locus was detected in up to 60% of CA cases. The in silico gene array analysis of CA showed down-regulation of DICER1 and an up-regulation of PRKRA. Immunohistochemically, DICER1 expression was abnormal in 65% of CA (95 of 147 cases). PRKRA was deregulated in 70% of CA (32 of 46 cases). Expression of DICER1 and PRKRA was correlated with clinicopathologic features of CA. DICER1 up-regulation was seen more commonly in women. Only 10 of 46 cases immunostained for both DICER1 and PRKRA showed normal levels of both DICER1 and PRKRA. Microsatellite status of 32 cases was determined. Microsatellite instable cases showed DICER1 up-regulation more commonly when compared to microsatellite stable cases; however, this trend was not statistically significant. Abnormal DICER1 and/or PRKRA expression might explain the observed changes in microRNA profile. The status of the endogenous DICER1 and PRKRA in CA may help to predict the response to future RNA interference-based therapy.
Insights
Abnormal expression of DICER1 and PRKRA proteins, crucial for microRNA biogenesis, is common in colon adenocarcinoma (CA). This deregulation may impact microRNA profiles and predict treatment response.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA (miRNA) expression is altered in colon adenocarcinoma (CA).
- DICER1 and PRKRA are key proteins in miRNA biogenesis.
- Loss of heterozygosity at the DICER1 locus is frequent in CA.
Purpose of the Study:
- To investigate the expression patterns of DICER1 and PRKRA in CA.
- To correlate DICER1 and PRKRA expression with clinicopathological features and microsatellite status.
- To assess the potential of DICER1 and PRKRA status as predictive biomarkers for RNA interference-based therapy.
Main Methods:
- In silico gene array analysis for DICER1 and PRKRA expression.
- Immunohistochemical analysis of DICER1 and PRKRA protein expression in CA tissues.
- Correlation analysis with clinicopathological parameters and microsatellite instability.
Main Results:
- Down-regulation of DICER1 and up-regulation of PRKRA observed in silico.
- Abnormal DICER1 expression in 65% and PRKRA deregulation in 70% of CA cases.
- Expression abnormalities correlated with clinicopathological features; DICER1 up-regulation more frequent in women.
- Microsatellite instable cases showed a non-significant trend towards DICER1 up-regulation.
Conclusions:
- Aberrant expression of DICER1 and PRKRA is a common feature in colon adenocarcinoma.
- These expression changes may underlie altered miRNA profiles in CA.
- DICER1 and PRKRA status could serve as predictive markers for RNA interference therapies in CA.
