Oxidative Stress–MicroRNA Interactions in Colorectal Cancer and Their Possible Relationships with Estrogen Receptor β

The pathogenesis of colorectal cancer (CRC) is characterized by significant alterations in redox homeostasis, epigenetic regulation and hormone-dependent signaling pathways. Oxidative stress (OS) promotes DNA damage, genomic instability, chronic inflammation, and the activation of several signaling pathways. Furthermore, dysregulation of various microRNAs (miRs) increases proliferation, invasion, metastasis, epithelial–mesenchymal transition, and angiogenesis, and promotes resistance to apoptosis and therapy. Increasing data suggest that there is a two-way interaction between reactive oxygen species (ROS) and miRs, where OS can influence the expression of miRs and, at the same time, miRs can affect intracellular redox state. This interrelationship plays a role in CRC initiation, development, and response to treatment. Estrogen receptor beta (ERβ) represents one of the defensive elements in the development of CRC. Its expression gradually decreases in colorectal cancerogenesis; conversely, its activation suppresses inflammation, proliferation, migration, invasion, and angiogenesis, and enhances apoptosis and DNA repair. In addition, ERβ is capable of modulating the expression of different miRs related to CRC and is involved in the modulation of the intracellular redox state. Limited and often indirect data indicate the role played by miRs and OS in regulating ERβ expression and vice versa. However, disturbing the complex regulatory network involving OS, miRNAs and ERβ may favor CRC development, while restoring it may represent a promising therapeutic strategy.