HPV-associated penile cancer: Impact of copy number alterations in miRNA/mRNA interactions and potential druggable targets

Article type: Research Article

Authors: Silva, Jenilson da^a | Nogueira, Leudivan^{a; b} | Coelho, Ronald^b | Deus, Amanda^{a; b} | Khayat, André^c | Marchi, Rafael^d | Oliveira, Edivaldo de^e | Santos, Ana Paula dos^f | Cavalli, Luciane^d | Pereira, Silma^{g; *}

Affiliations: [a] Postgraduate Program in Health Science, Federal University of Maranhão, São Luís, MA, Brazil | [b] Aldenora Bello Cancer Hospital, São Luís, MA, Brazil | [c] Oncology Research Center, Federal University of Pará, Belém, PA, Brazil | [d] Research Institute Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, Curitiba, PR, Brazil | [e] Tissue Culture and Cytogenetics Laboratory, Institute of Evandro Chagas, Belém, PA, Brazil | [f] Department of Physiological Sciences, Federal University of Maranhão, São Luís, MA, Brazil | [g] Laboratory of Genetics and Molecular Biology, Department of Biology, Federal University of Maranhão, São Luís, MA, Brazil

Correspondence: [*] Corresponding author: Silma Regina Ferreira Pereira, Laboratory of Genetics and Molecular Biology, Department of Biology, Federal University of Maranhão, 1966, Avenida dos Portugueses, São Luís, MA, Brazil. Tel.: +55 98 32729576; E-mail: [email protected].

Abstract: BACKGROUND: Penile cancer (PeCa) is a rare disease, but its incidence has increased worldwide, mostly in HPV+ patients. Nevertheless, there is still no targeted treatment for this carcinoma. OBJECTIVE: To predict the main signaling pathways involved in penile tumorigenesis and its potential drug targets. METHODS: Genome-wide copy number profiling was performed in 28 PeCa. Integration analysis of CNAs and miRNAs and mRNA targets was performed by DIANA-TarBase v.8. The potential impact of the miRNAs/target genes on biological pathways was assessed by DIANA-miRPath v.3.0. For each miRNA, KEGG pathways were generated based on the tarbase and microT-CDS algorithms. Pharmaco-miR was used to identify associations between miRNAs and their target genes to predict druggable targets. RESULTS: 269 miRNAs and 2,395 genes were mapped in cytobands with CNAs. The comparison of the miRNAs mapped at these cytobands and the miRNAs that were predicted to regulate the genes also mapped in these regions, resulted in a set of common 35 miRNAs and 292 genes. Enrichment pathway revealed their involvement in five top signaling pathways. EGFR and COX2 were identified as potential druggable targets. CONCLUSION: Our data indicate the potential use of EGFR and COX2 inhibitors as a target treatment for PeCa patients.

Keywords: Genomic profiling, molecular target, biomarkers, human papillomavirus, penile tumor

DOI: 10.3233/CBM-210035

Journal: Cancer Biomarkers, vol. 32, no. 2, pp. 147-160, 2021