Open AccessSAP 155‐mediated c‐myc suppressor far‐upstream element‐binding protein‐interacting repressor splicing variants are activated in colon cancer tissues
Author(s) -
Kajiwara Toshiko,
Matsushita Kazuyuki,
Itoga Sakae,
Tamura Mai,
Tanaka Nobuko,
Tomonaga Takeshi,
Matsubara Hisahiro,
Shimada Hideaki,
Habara Yasuaki,
Matsuo Masafumi,
Nomura Fumio
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12058
Subject(s) - colorectal cancer , rna splicing , cancer research , exon , carcinoembryonic antigen , alternative splicing , repressor , gene knockdown , microbiology and biotechnology , medicine , biology , cancer , transcription factor , gene , genetics , rna
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 SAP 155 pre‐ mRNA ‐splicing factor, a subunit of SF 3b, was reported to disturb FIR pre‐ mRNA splicing and yield FIR Δexon2, 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 SAP 155 si RNA , 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 , FIR Δexon2 or FIR Δexon2/ FIR , was greater than those of conventional carcinoembryonic antigen or carbohydrate antigen 19‐9. In addition, FIR Δexon2 or FIR mRNA expression in the peripheral blood was significantly reduced after operative removal of colorectal tumors. Thus, circulating FIR and FIR Δexon2 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.