The multifaceted role of microRNAs in colorectal cancer: pathogenesis and therapeutic implications

Abstract

MicroRNAs (miRNAs) are important regulators of gene expression and their dysregulation is involved in various diseases, including tumors. Among these, colorectal cancer (CRC) is the result of both genetic and epigenetic alterations with miRNAs playing a key pathogenetic role. Although numerous studies have investigated the most frequently dysregulated miRNAs in CRC, there is still no consensus on the specific role of individual miRNAs in the mechanisms leading to tumorigenesis, tumor progression, and the development of chemoresistance. This lack of clarity highlights the need for a deeper understanding of miRNA functions in CRC. Therefore, this review aims to clarify the role of miRNAs in CRC by examining their involvement in major oncogenic pathways, highlighting key miRNAs implicated in the disease, and exploring their potential as diagnostic biomarkers and therapeutic targets. By providing a comprehensive overview, we hope to shed light on the complex and multifaceted roles of miRNAs in CRC, which could pave the way for more effective CRC monitoring and the development of miRNA-guided therapeutic strategies.

Keywords: Biomarker; Colorectal cancer; Drug resistance; Epigenetics; Therapeutic target; microRNA.

Fig. 1

Several strategies are available to modulate the levels of miRNAs in the cell. Small miRNA inhibitors (SMIRs) can inhibit the activity of miRNAs by hindering steps in their biogenesis. Antisense oligonucleotides (ASOs), anti-microRNA ASOs (antimiRs) or miRNA sponges are molecules that inhibit miRNA function while small interfering RNAs (siRNAs), short hairpin RNAs (shRNAs) or mimic miRNAs are molecules that mimic miRNA activity.