Dec 18, 2013

Tumor microenvironment-associated modifications of alternative splicing

Jean-Philippe BrosseauSherif Abou-Elela


Pre-mRNA alternative splicing is modified in cancer, but the origin and specificity of these changes remain unclear. Here, we probed ovarian tumors to identify cancer-associated splicing isoforms and define the mechanism by which splicing is modified in cancer cells. Using high-throughput quantitative PCR, we monitored the expression of splice variants in laser-dissected tissues from ovarian tumors. Surprisingly, changes in alternative splicing were not limited to the tumor tissues but were also found in the tumor microenvironment. Changes in the tumor-associated splicing events were found to be regulated by splicing factors that are differentially expressed in cancer tissues. Overall, ∼20% of the alternative splicing events affected by the down-regulation of the splicing factors QKI and RBFOX2 were altered in the microenvironment of ovarian tumors. Together, our results indicate that the tumor microenvironment undergoes specific changes in alternative splicing orchestrated by a limited number of splicing factors.

Mentioned in this Paper

Ovarian Diseases
Nested Transcripts
Cancer Microenvironment
Tissue Specificity
Ovarian Neoplasm
Gene Expression
Repressor Molecules
RNA Splice Sites
Heterogeneous Nuclear RNA

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