A. Aksoy, A. Varoğlu, E. Onalan, A. Tektemur, G. Artas
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Research Article siRNA-mediated mesothelin silencing for treatment of mesothelioma
It is known that mesothelin (MSLN) is overexpressed in some cancers, and that it plays a role in cell growth through Wnt family member 1 protein. Malignant transformation usually occurs with disruption of autoregulation of autophagy-related genes. We examined the effect of MSLN on survival and clinicopathological features in mesothelioma cases, as well as variations in genes associated with autophagy, invasion, apoptosis-related genes after siRNA-mediated MSLN silencing transfection in a mesothelioma cell line (SPC212). MSLN expression was analyzed, immunohistochemically, in formalinfixed paraffin-embedded 60 mesothelioma cases. MSLN expression was categorized by median MSLN histoscores as low (L), high (H). The correlation between the levels of MSLN expression, clinicopathological features, and survival was determined in mesothelioma cases. The siRNA-mediated MSLN incubated SPC212 cells were transfected and compared to negative control siRNAs. mRNA levels were determined for autophagy, invasion, and apoptosis related-genes with RT-PCR, and western blotting in SPC212 cells after MSLN silencing. All of the cases were immunoreactive for MSLN expression. H-MSLN was associated with a favorable prognosis according to Kaplan-Meier survival analysis, but Cox regression analysis revealed that only stage was a significant independent factor for estimating survival. MSLN overexpression was
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Genetics and Molecular Research (GMR), maintained by the Research Foundation of Ribeirão Preto (Fundação de Pesquisas Científicas de Ribeirão Preto), publishes high quality research in genetics and molecular biology. GMR reflects the full breadth and interdisciplinary nature of this research by publishing outstanding original contributions in all areas of biology.
GMR publishes human studies, as well as research on model organisms—from mice and flies, to plants and bacteria. Our emphasis is on studies of broad interest that provide significant insight into a biological process or processes. Topics include, but are not limited to gene discovery and function, population genetics, evolution, genome projects, comparative and functional genomics, molecular analysis of simple and complex genetic traits, cancer genetics, medical genetics, disease biology, agricultural genomics, developmental genetics, regulatory variation in gene expression, pharmacological genomics, evolution, gene expression, chromosome biology, and epigenetics.
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