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Figure 2. (A) Elevated expression of c-Myc has been detected in a broad range of human cancers, indicating a key role for this oncogene in tumor development. Far upstream element-binding protein-interacting repressor (FIR) gen and c-Myc gene locates at 8q24.3. An interaction between FIR (FBP interacting repressor) and transcriptional factor IIH helicase was found to repress c-Myc transcription and so might be important for suppressing tumor formation. FIR is alternatively spliced in colorectal cancer lacking the transcriptional repression domain within exon 2 (FIRΔexon2) that inhibit FIR as a dominant negative form of FIR. FIRΔexon2 potently forms a heterodimer with FIR and thus FIRΔexon2 interferes with FIR to bind to far upstream element of c-Myc promoter where FIR binds. FIR and FIRΔexon2 form a homo- or hetero-dimer, which makes a complex with SAP155. SAP155 is a subunit of the essential splicing factor 3B (SF3B) subcomplex in the spliceosome. The interaction between SAP155 and FIR/FIRΔexon2 potentially integrated cell cycle progression and c-Myc transcription through P89 suppression; (B) FIR/FIRΔexon2/SAP155 interaction is pivotal for cancer development and differentiation and is thus a potent target for cancer screening and treatment. These results strongly suggest that FIRΔexon2 antagonized FIR in c-Myc transcriptional suppression and simultaneously interferes with SF3B in splicing during tumor progression. Importantly, Spliceostatin A that is a strong chemical inhibitor of SF3B resulted in c-Myc overexpression probably due to the FIR downregulation. FIR: FUBP1-interacting repressor