Portrait of Cancer Stem Cells on Colorectal Cancer: Molecular Biomarkers, Signaling Pathways and miRNAome

Abstract: Colorectal cancer (CRC) is a leading cause of cancer death worldwide, and about 20% is
metastatic at diagnosis and untreatable. Increasing evidence suggests that the heterogeneous nature
of CRC is related to colorectal cancer stem cells (CCSCs), a small cells population with stemness
behaviors and responsible for tumor progression, recurrence, and therapy resistance. Growing
knowledge of stem cells (SCs) biology has rapidly improved uncovering the molecular mechanisms
and possible crosstalk/feedback loops between signaling pathways that directly influence intestinal
homeostasis and tumorigenesis. The generation of CCSCs is probably connected to genetic changes
in members of signaling pathways, which control self-renewal and pluripotency in SCs and then
establish function and phenotype of CCSCs. Particularly, various deregulated CCSC-related miRNAs
have been reported to modulate stemness features, controlling CCSCs functions such as regulation of
cell cycle genes expression, epithelial-mesenchymal transition, metastasization, and drug-resistance
mechanisms. Primarily, CCSC-related miRNAs work by regulating mainly signal pathways known
to be involved in CCSCs biology. This review intends to summarize the epigenetic findings linked to
miRNAome in the maintenance and regulation of CCSCs, including their relationships with different
signaling pathways, which should help to identify specific diagnostic, prognostic, and predictive
biomarkers for CRC, but also develop innovative CCSCs-targeted therapies.