Leão Stephanie Loureiro, Parente da Silva Gabriel Rômulo, Dos Santos Daffany Luana, São Marcos Bianca de França, Bezerra Fontes Pedro Henrique, de Oliveira Isídio Beatriz Eda, Simões Isabelle Silva, Genn Barros Elisa Fotin, Lussón David Beltrán, Crispim Joelson Germano, Leal Lígia Rosa Sales, Silva Anna Jéssica Duarte, Pereira Santos Vanessa Emanuelle, de Freitas Antonio Carlos
Laboratory of Molecular Studies and Experimental Therapy, Department of Genetics, Federal University of Pernambuco, Av. Prof. Moraes Rego, 1235. Cidade Universitária Recife, Recife 50670-901, Pernambuco, Brazil.
Laboratory for Immunomodulation and New Therapeutic Approaches, Research Center for Therapeutic Innovation, Federal University of Pernambuco, Recife 50670-901, Pernambuco, Brazil.
Viruses. 2025 Jun 23;17(7):880. doi: 10.3390/v17070880.
Breast cancer is among the most prevalent and deadly types of cancer worldwide. Viral infections have been investigated as contributing factors in breast carcinogenesis, including infections by high-risk genotypes of human papillomavirus (HPV). Although viral DNA has been detected in breast tumors, the role of HPV activity in this type of cancer remains poorly understood. HPV oncogenes interact with various host genes, including those involved in the JAK/STAT signaling pathway. This pathway is associated with the regulation of gene expression related to the tumor microenvironment, and understanding how HPV oncogenes interact with JAK/STAT components may provide insights into the relationship between the virus and breast cancer development. In this study, we assessed the differential expression of the JAK/STAT pathway in MDA-MB-231 cells individually transfected with the E5, E6, and E7 oncogenes of HPV16. The results revealed downregulation of STAT4 in the presence of the E5, E6, and E7 oncogenes. Notably, cells transfected with E5 alone exhibited upregulation of JAK2, STAT3, and STAT6, whereas transfection with E6 and E7 resulted in their downregulation. These findings highlight the underexplored role of the E5 oncogene in contrast to the more extensively studied E6 and E7. Our results support the hypothesis that HPV oncogenes actively modulate the expression of genes involved in the tumor microenvironment in breast cancer.
乳腺癌是全球最常见且致命的癌症类型之一。病毒感染已被研究为乳腺癌发生的促成因素，包括高危基因型人乳头瘤病毒（HPV）的感染。尽管在乳腺肿瘤中已检测到病毒DNA，但HPV活性在这类癌症中的作用仍知之甚少。HPV癌基因与多种宿主基因相互作用，包括那些参与JAK/STAT信号通路的基因。该通路与肿瘤微环境相关基因表达的调控有关，了解HPV癌基因如何与JAK/STAT组分相互作用可能有助于深入了解病毒与乳腺癌发展之间的关系。在本研究中，我们评估了单独转染HPV16的E5、E6和E7癌基因的MDA-MB-231细胞中JAK/STAT通路的差异表达。结果显示，在存在E5、E6和E7癌基因的情况下，STAT4表达下调。值得注意的是，单独转染E5的细胞中JAK2、STAT3和STAT6表达上调，而转染E6和E7则导致它们表达下调。这些发现突出了与研究更广泛的E6和E7相比，E5癌基因尚未得到充分探索的作用。我们的结果支持这样的假设，即HPV癌基因积极调节乳腺癌中参与肿瘤微环境的基因表达。
