Furuya Tatiane Katsue, Murta Claudio Bovolenta, Murillo Carrasco Alexis Germán, Uno Miyuki, Sichero Laura, Villa Luisa Lina, Cardilli Leonardo, Coelho Rafael Ferreira, Guglielmetti Giuliano Betoni, Cordeiro Mauricio Dener, Leite Katia Ramos Moreira, Nahas William Carlos, Chammas Roger, Pontes José
Center for Translational Research in Oncology (LIM24), Instituto do Cancer do Estado de Sao Paulo (ICESP), Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), Sao Paulo CEP 01246-000, SP, Brazil.
Departamento de Urologia, ICESP, HCFMUSP, Sao Paulo CEP 01246-000, SP, Brazil.
Cancers (Basel). 2021 Sep 23;13(19):4745. doi: 10.3390/cancers13194745.
Penile cancer (PeC) carcinogenesis is not fully understood, and no biomarkers are reported in clinical practice. We aimed to investigate molecular signatures based on miRNA and mRNA and perform an integrative analysis to identify molecular drivers and pathways for PeC development. Affymetrix miRNA microarray was used to identify differentially expressed miRNAs (DEmiRs) comparing 11 tumoral tissues (TT) paired with non-neoplastic tissues (NNT) with further validation in an independent cohort ( = 13). We also investigated the mRNA expression of 83 genes in the total sample. Experimentally validated targets of DEmiRs, miRNA-mRNA networks, and enriched pathways were evaluated in silico. Eight out of 69 DEmiRs identified by microarray analysis were validated by qRT-PCR (miR-145-5p, miR-432-5p, miR-487b-3p, miR-30a-5p, miR-200a-5p, miR-224-5p, miR-31-3p and miR-31-5p). Furthermore, 37 differentially expressed genes (DEGs) were identified when comparing TT and NNT. We identified four downregulated DEmiRs (miR-30a-5p, miR-432-5p, miR-487b-3p, and miR-145-5p) and six upregulated DEGs (, , , , and ) as potential biomarkers in PeC by their capacity of discriminating TT and NNT with accuracy. The integration analysis showed eight dysregulated miRNA-mRNA pairs in penile carcinogenesis. Taken together, our findings contribute to a better understanding of the regulatory roles of miRNAs and altered transcripts levels in penile carcinogenesis.
阴茎癌（PeC）的致癌机制尚未完全明确，临床实践中也未报告有生物标志物。我们旨在研究基于miRNA和mRNA的分子特征，并进行综合分析以确定阴茎癌发生发展的分子驱动因素和相关通路。使用Affymetrix miRNA微阵列来鉴定差异表达的miRNA（DEmiRs），比较11对肿瘤组织（TT）与非肿瘤组织（NNT），并在一个独立队列（n = 13）中进行进一步验证。我们还研究了总样本中83个基因的mRNA表达。通过计算机模拟评估了DEmiRs的实验验证靶点、miRNA-mRNA网络和富集通路。通过微阵列分析鉴定出的69个DEmiRs中有8个通过qRT-PCR得到验证（miR-145-5p、miR-432-5p、miR-487b-3p、miR-30a-5p、miR-200a-5p、miR-224-5p、miR-31-3p和miR-31-5p）。此外，比较TT和NNT时鉴定出37个差异表达基因（DEGs）。我们通过区分TT和NNT的能力，确定了四个下调的DEmiRs（miR-30a-5p、miR-432-5p、miR-487b-3p和miR-145-5p）和六个上调的DEGs（、、、、和）作为阴茎癌的潜在生物标志物。综合分析显示阴茎癌发生过程中有八对失调的miRNA-mRNA对。综上所述，我们的研究结果有助于更好地理解miRNA的调控作用以及阴茎癌发生过程中转录本水平的改变。
