MicroRNAs are related to human cancers, including cervical Background cancer (CC) caused by HPV. In 2018, approximately 56.075 cases and 28.252 deaths from this cancer were registered in Latin America and the Caribbean according to GLOBOCAN reports. 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).: The miRNAs associated with CC were obtained from literature, Methods the miRNA sequences and four human genome variants (HGV) from Latin American populations were obtained from miRBase and 1000 Genomes Browser, respectively. HPV integration sites near cell cycle regulatory genes were identified. miRNAs were mapped on HGV. miRSNPs were identified in the miRNA sequences located at HPV integration sites on the Latin American HGV.: Two hundred seventy-two miRNAs associated with CC were Results identified in 139 reports from different geographic locations. By mapping with 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 Latin American HGV (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.: Ten miRNAs were conserved in the four HGV. In the Conclusions remaining 27 miRNAs, substitutions, deletions or insertions were observed. These variation patterns can imply differentiated mechanisms towards each genomic variant in human populations because of specific genomic patterns and geographic features. These findings may help in determining susceptibility for CC development. Further identification of cellular genes
ResumenIntroducción: Los miRNAs tienen especial interés en oncología por su papel en el control de la expresión de genes reguladores del ciclo celular, alteración génica y su implicación en diferentes tipos de cáncer, tales como el cáncer de cuello uterino (CCU). Materiales y métodos: Se realizó una búsqueda sistemática de literatura científica, en bases de datos, donde establecieran asociación de miRNAs con CCU. Se analizó la localización genómica y cromosómica de miRNAs, la clasificación funcional, grupos de miRNAs al que pertenecen y su implicación en la progresión de este cáncer. Resultados: Se incluyeron 139 artículos científicos sobre miRNAs relacionados al CCU. Se identificó un total de 272 miRNAs, de los cuales 252 miRNAs con expresión diferencial en tejidos con CCU: 97 sobre-expresados, 88 infraexpresados y 67 miRNAs con perfiles de expresión variable. La mayoría de miRNAs asociados al CCU se encontraron en los cromosomas 1, 14, 19 y X, así como en regiones intrónicas e intergénicas. Se identificaron miRNAs en procesos asociados al control del ciclo celular. Conclusión: Con esta revisión se destaca la importancia de miRNAs como potenciales biomarcadores pronóstico y diagnóstico, se brinda una actualización sobre miRNAs asociados al CCU y sus lesiones precursoras y se genera un recurso de recopilación y consulta valioso para orientar futuras investigaciones de medicina molecular en este campo. Se recomiendan más estudios experimentales para esclarecer los mecanismos de los miRNAs en desarrollo del CCU.Palabras clave: Cáncer de cuello uterino; microRNAs; biomarcadores; diagnóstico; biología molecular. (Fuente: DeCS, Bireme). AbstractIntroduction: MicroRNAs (miRNAs) have special interest in oncology because of its role in the control of the expression of cell cycle regulatory genes, gene alterations and its involvement on different types of cancer such as cervical cancer (CC). Materials and methods: A systematic literature search was performed using different databases to establish relationship of miRNAs with UCC. Genomic and chromosomic location of miRNAs were analyzed along with its functional classification, miRNAs groups they belong to, and possible roles in progression of the disease. Results: 139 scientific articles about the role of miRNAs in CC were included. A total of 272 miRNA were
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.
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