Cancer development by the human papillomavirus (HPV) infection can occur through the canonical HPV/p53/RB1 pathway mediated by the E2/E6/E7 viral oncoproteins. During the transformation process, HPV inserts its genetic material into host Integration Sites (IS), affecting coding genes and miRNAs. In penile cancer (PeCa) there is limited data on the miRNAs that regulate mRNA targets associated with HPV, such as the TP53 and RB1 genes. Considering the high frequency of HPV infection in PeCa patients in Northeast Brazil, global miRNA expression profiling was performed in high-risk HPV-associated PeCa that presented with TP53 and RB1 mRNA downregulated expression. The miRNA expression profile of 22 PeCa tissue samples and five non-tumor penile tissues showed 507 differentially expressed miRNAs: 494 downregulated and 13 upregulated (let-7a-5p, miR-130a-3p, miR-142-3p, miR-15b-5p miR-16-5p, miR-200c-3p, miR-205-5p, miR-21-5p, miR-223-3p, miR-22-3p, miR-25-3p, miR-31-5p and miR-93-5p), of which 11 were identified to be in HPV16-IS and targeting TP53 and RB1 genes. One hundred and thirty-one and 490 miRNA binding sites were observed for TP53 and RB1, respectively, most of which were in seedless regions. These findings suggest that up-regulation of miRNA expression can directly repress TP53 and RB1 expression by their binding sites in the non-canonical seedless regions.
Frontiers in genetics. 2022 Jun 24*** epublish ***
Jenilson da Silva, Carla Cutrim da Costa, Ingryd de Farias Ramos, Ana Carolina Laus, Luciane Sussuchi, Rui Manuel Reis, André Salim Khayat, Luciane Regina Cavalli, Silma Regina Pereira
Postgraduate Program in Health Science, Federal University of Maranhão, São Luís, Brazil., Degree in Biological Sciences, Department of Biology, Federal University of Maranhão, São Luís, Brazil., Postgraduate Program in Oncology and Medical Sciences, Federal University of Pará, Belém, Brazil., Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Brazil., Oncology Research Center, Federal University of Pará, Belém, Brazil., Research Institute Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Curitiba, Brazil., Laboratory of Genetics and Molecular Biology, Department of Biology, Federal University of Maranhão, São Luís, Brazil.