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

Jaqueline Mena Huertas,Milena Guerrero Flórez,Olivia Alexandra Guerrero Gómez,María Clara Yépez Chamorro

doi:10.12688/f1000research.10138.1

Abstract

Background: MicroRNAs are related to human cancers, including cervical 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). Methods: miRNA sequences associated with CC and four human genome 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. Results: Two hundred seventy-two miRNAs associated with CC were 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. Conclusions: 10 miRNAs were conserved in the four human genome variants, 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.

Highlights

Cervical cancer (CC) is the second most common malignancy in women worldwide
Five hundred and seventy-eight integration sites for 8 types of human papillomavirus (HPV) associated with different histological cervical conditions were identified, of which 63.84% were HPV-16 (Figure 2 and ‘HPV integration sites’ in Dataset 236)
HPV integration sites According to the literature, approximately 570 integration sites have been identified for eight oncogenic HPV types associated with CC (Figure 2)

Summary

Introduction

Cervical cancer (CC) is the second most common malignancy in women worldwide. According to GLOBOCAN reports, approximately 530,000 women are diagnosed with CC and 265,672 die from it each year. MiRNAs are a class of small (18 to 26 nucleotides length), noncoding, evolutionarily conserved RNAs that are processed from longer transcripts known as pre-miRNAs (60 to 100 nucleotides in length)10 They are located on regions known as fragile sites and distributed in intergenic, intronic and exonic segments of the human genome involved in cancer. MiRSNPs (single nucleotide polymorphisms in miRNAs) were identified in the miRNA sequences located at HPV integration sites on the human genomic Latin American variants. 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. This variability can imply differentiated mechanisms towards each genomic variant in human populations, relative to specific genomic patterns and geographic features

Objectives

Methods

Results

Conclusion