B-377 Mirsnps as Potential Colorectal Cancer Biomarkers: An Overview
Authors: Santos Silva C , Alves dos Santos K , Costa de Souza K , Nogueira Silbiger V , Ducati Luchessi A 
Published: September 2023

Abstract

Background
Colorectal cancer (CRC), also known as colon cancer, is a neoplasm that affects the colon (large intestine) or rectum. CRC stands out for being the third most frequent neoplasm in the world population, being the second cancer with the highest mortality rate. Single nucleotide polymorphisms (SNPs) located in miRNAs genes, known as miRSNPs, may be associated with dysregulated expression of miRNAs in neoplasms. The objective of this review was to highlight the SNPs that alter the biogenesis or processing of miRNAs associated with CRC as potential biomarkers of this disease, according to the literature.

Methods
A search of original articles in the literature was performed in PubMed, Embase and Web of Science databases. The bibliographic search included scientific articles published between 2008 and 2022, with the objective of investigating associations between miRSNPs and CRC. Exclusion criteria were brief communications and other reviews on the subject. A total of 263 articles were detected in the preliminary search, of which 133 were excluded for being replicated, 34 for being reviewers, 3 for being paid and 40 for dealing with other subjects. Thus, of the remaining 53 studies, 35 were excluded after reading because they included studies that described SNPs located in miRNA genes and SNPs located in miRNA binding sites. Finally, 18 articles that included SNPs located in the regulatory regions of miRNAs were selected for this review. The list of genes generated for each of the targets was performed using the online tool miRBase and miRDB, for prediction of miRNA targets and functional annotations. The miRTarBase online database was consulted to select target miRNAs and possible interactions. By crossing the list of genes targeted by miRNAs to identify the biological pathways, those with the greatest biological relevance were chosen using the Enrichr online tool.

Results
This review covered 18 studies related to SNPs located in regulatory regions of mature miRNAs that may influence the occurrence and progression of CRC. In order to characterize the metabolic profile induced by each target of the miRNAs selected in this review, it was possible to observe that miR-196, miR-211, miR-30a, miR-143, miR-27 and miR-146a are more strongly associated with positive regulation of transcription. Cytokine-mediated signaling pathway and regulation of cell migration were most strongly associated with miR-143 and miR-146a. Furthermore, it was identified that the upregulation of the apoptosis process was strongly associated with miR-30a, miR-143, miR-27a and miR-146a. MiR-211, miR-143, mi-27a and miR-146a were strongly associated with the upregulation of cell proliferation. Finally, with the objective of evaluating the correlation between the selected miRNAs. It was possible to observe a greater correlation between miR-27a and miR-30a.

Conclusion
Studies related to miRSNPs have been of great interest in recent years in order to find promising and less invasive new biomarkers, sensitive and specific for the early detection of CRC. Our study aims to help better understand the pathways that cause the development of CRC and possible biomarkers to predict its development and consequently reduce morbidity and mortality and improve patient survival.