Interrelationship between microsatellite instability and microRNA in gastrointestinal cancer

Figure 1 A model of DNA mismatch repair and molecular pathways for microsatellite instability+ colorectal cancers. A: A model of the proposed mechanism of mismatch repair (MMR) proteins, illustrating patterns of relevant heterodimerization; B: The models for colorectal cancer (CRC) carcinogenesis are presented in parallel for Lynch syndrome and sporadic cases. HNPCC: Hereditary nonpolyposis colorectal cancer; MSI: Microsatellite instability; CIMP: CpG island methylator phenotype; MSI: Microsatellite instability.

Figure 2 Cancer progression of sporadic microsatellite instability+ colorectal cancers. The model for microsatellite instability (MSI)+ colorectal cancer progression is presented based on levels of MSI and chromosomal instability (CIN), and genetic, epigenetic and miRNA alterations. SSA/P: Sessile serrated adenomas/polyps; CIMP: CpG island methylator phenotype; MMR: Mismatch repair.

Figure 3 Representative target genes in microsatellite instability+ gastrointestinal cancers. A number of cancer-related genes mutated in microsatellite instability+ gastrointestinal cancers have been reported. The relevance of each mutation is not necessarily proven.

Figure 4 MiRNA biogenesis and genes mutated in microsatellite instability+ gastrointestinal cancers. A consequence of perfect complementarity between miRNA and mRNA is mRNA cleavage and degradation. Imperfect alignment represses gene translation. ORF: Open reading frame; RISC: RNA-induced silencing complexes.

Figure 5 Targeted therapies based on molecular alterations in microsatellite instability+ colorectal cancers. Microsatellite instability+ cancers may be managed more effectively with novel targeted therapies based on molecular alterations. MSI: Microsatellite instability; HDAC: Histone deacetylase; PI3K/mTOR: Phosphoinositide 3-kinase/mammalian target of rapamycin; XPO5: Exportin 5.