Mapping of microRNAs related to cervical cancer in Latin American human genomic variants

Abstract

MicroRNAs are related to human cancers, including cervical Background cancer (CC), which is mainly caused by human papillomavirus (HPV) infection. In 2012, approximately 70000 cases and 28000 deaths from this cancer were registered in Latin America according to GLOBOCAN reports. The most frequent genotype worldwide is HPV-16. The main molecular mechanism of HPV in CC is related to integration of viral DNA into the hosts' genome. However, the different variants in the human genome can result in different integration mechanisms, specifically involving microRNAs (miRNAs).: miRNA sequences associated with CC and four human genome Methods variants from Latin American populations were obtained from miRBase and the 1000 Genomes Browser, respectively. HPV integration sites near cell cycle regulatory genes were identified. miRNAs were mapped on human genomic variants. miRSNPs (single nucleotide polymorphisms in miRNAs) were identified in the miRNA sequences located at HPV integration sites on the human genomic Latin American variants.: Two hundred seventy-two miRNAs associated with CC were Results identified in 139 reports from different geographic locations. By mapping with the Blast-Like Alignment Tool (BLAT), 2028 binding sites were identified from these miRNAs on the human genome (version GRCh38/hg38); 42 miRNAs were located on unique integration sites; and miR-5095, miR-548c-5p and miR-548d-5p were involved with multiple genes related to the cell cycle. Thirty-seven miRNAs were mapped on the human Latin American genomic variants (PUR, MXL, CLM and PEL), but only miR-11-3p, miR-31-3p, miR-107, miR-133a-3p, miR-133a-5p, miR-133b, miR-215-5p, miR-491-3p, miR-548d-5p and miR-944 were conserved.: 10 miRNAs were conserved in the four human genome variants, Conclusions and in the remaining 27 miRNAs, substitutions, deletions or insertions were observed in the nucleotide sequences. This variability can imply differentiated mechanisms towards each genomic variant in human populations, relative to specific genomic patterns and geographic features. These findings may be decisive in determining susceptibility to the development of CC. Further identification of cellular genes and signalling pathways involved in CC progression could lead to the development of new therapeutic strategies based on miRNAs.