SAP155-mediatedc-mycsuppressor far-upstream element-binding protein-interacting repressor splicing variants are activated in colon cancer tissues
Autor: | Yasuaki Habara, Mai Tamura, Masafumi Matsuo, Hideaki Shimada, Nobuko Tanaka, Toshiko Kajiwara, Sakae Itoga, Fumio Nomura, Takeshi Tomonaga, Kazuyuki Matsushita, Hisahiro Matsubara |
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Rok vydání: | 2012 |
Předmět: |
Transcriptional Activation
RNA Splicing Factors Cancer Research Transcription Genetic Colorectal cancer RNA Splicing Repressor Biology Proto-Oncogene Proteins c-myc Carcinoembryonic antigen Cell Line Tumor Chlorocebus aethiops Biomarkers Tumor RNA Precursors medicine Animals Guanine Nucleotide Exchange Factors Humans Protein Isoforms Antigens Tumor-Associated Carbohydrate Genes Tumor Suppressor RNA Messenger RNA Small Interfering Messenger RNA Gene knockdown Alternative splicing Exons Original Articles General Medicine Ribonucleoprotein U2 Small Nuclear HCT116 Cells Phosphoproteins medicine.disease Alternative Splicing Oncology COS Cells Colonic Neoplasms Immunology RNA splicing biology.protein Cancer research Rho Guanine Nucleotide Exchange Factors HeLa Cells |
Zdroj: | Cancer Sci |
ISSN: | 1347-9032 |
Popis: | The c‐myc transcriptional suppressor, far‐upstream element (FUSE)‐binding protein (FBP)‐interacting repressor (FIR), is alternatively spliced in colorectal cancer tissue (Matsushita et al., Cancer Res 2006). Recently, the knockdown of SAP155 pre‐mRNA‐splicing factor, a subunit of SF3b, was reported to disturb FIR pre‐mRNA splicing and yield FIRΔexon2, an exon 2‐spliced variant of FIR, which lacks c‐myc repression activity. In the present study, novel splicing variants of FIR, Δ3 and Δ4, were also generated by SAP155 siRNA, and these variants were found to be activated in human colorectal cancer tissue. Furthermore, the expression levels of FIR variant mRNA were examined in the peripheral blood of colorectal cancer patients and healthy volunteers to assess its potency for tumor detection. As expected, circulating FIR variant mRNA in the peripheral blood of cancer patients were significantly overexpressed compared to that in healthy volunteers. In particular, the area under the receiving operating characteristic curve of FIR, FIRΔexon2 or FIRΔexon2/FIR, was greater than those of conventional carcinoembryonic antigen or carbohydrate antigen 19‐9. In addition, FIRΔexon2 or FIR mRNA expression in the peripheral blood was significantly reduced after operative removal of colorectal tumors. Thus, circulating FIR and FIRΔexon2 mRNA are potential novel screening markers for colorectal cancer testing with conventional carcinoembryonic antigen and or carbohydrate antigen 19‐9. Taken together, our results indicate that overexpression of FIR and its splicing variants in colorectal cancer directs feed‐forward or addicted circuit c‐myc transcriptional activation. Clinical implications for colorectal cancers of novel FIR splicing variants are also discussed in the present paper. |
Databáze: | OpenAIRE |
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