Dados do Resumo

Título

The changes in placental miRNA expression possibly impact biological processes of apoptosis and vascularization in pregnant patients with breast cancer

Introdução

Breast cancer during pregnancy (PrBC), followed by chemotherapy treatment, can result in damage to the placenta and, consequently, inadequate fetal development. Placental miRNAs play an important role in the regulation of trophoblast cell differentiation, migration, invasion, proliferation, apoptosis, vasculogenesis/angiogenesis and cellular metabolism. However, this role of altered miRNA in the placenta of patients with PrBC associated with chemotherapy is still unknown.

Objetivo

Therefore, we evaluated the influence of miRNAs, potential targets and the respective biological process in the placenta of patients with PrBC.

Métodos

Placentas from patients with PrBC who received chemotherapy treatment (case group, n= 7) and from patients with low-risk pregnancies (control group, n= 8) were obtained from the Center for Integral Attention to Women’s Health biobank of University of Campinas (CAAE: 65070122.0.0000.5404). Total RNA was extracted from the chorionic villi region of the placenta and subjected to cDNA synthesis. The expression of 384 human miRNAs was analysed by RT-qPCR. The data were normalized by the Quartile method, and the miRNAs miR-518a-5p_miR-527 and miR-660-5p were candidates as endogenous reaction controls by NormFinder algorithm. The expression of miRNAs was calculated by 2-ΔCT method and analysed by t-test and Mann-Whitney. The potential targets of miRNAs and Gene Ontology (biological process) were identified by bioinformatics tools in the miRWalk database and DAVID resources, respectively. For all statistical analyses, P< 0.05 was considered significant.

Resultados

32 miRNAs were differentially expressed, of which 13 were upregulated, and 19 were downregulated in the case group compared to the control group. Of the 13 miRNAs upregulated were identified 10,377 potential targets with impact on 572 biological processes: 39 related to apoptosis and 18 associated with vascularization. Interestingly, the miR-145-5p (Fold Change log2: 0.349, P= 0.011) and miR-542-5p (Fold Change log2: 1.546, P= 0.021) miRNAs had an impact of 41.0% and 38.4% on apoptosis and 27.7% and 5.5% on vascularization, respectively. On the other hand, of the 19 miRNAs downregulated were identified 10,732 potential targets with impact on 602 biological processes: 41 related to apoptosis and 23 associated with vascularization. Curiously, the miR-486-3p (Fold Change log2: -0.751, P= 0.023) and miR-485-5p (Fold Change log2: -0.421, P= 0.040) miRNAs exert an impact of 31.7% and 24.4% on apoptosis and 17.4% and 21.7% on vascularization, respectively.

Conclusões

Our findings suggest that miRNAs, especially the miR-145-5p, miR-542-5p, miR-486-3p and miR-485-5p, along with their potential targets, can modulate different biological processes, such as increased apoptosis and impaired vascularization, which can be associated with placental pathologies, leading to impairments to pregnancy course for patients with PrBC.

Financiador do resumo

FAPESP #2021/08931-0, #2023/01310-5 and #23/09611-4; CNPq #151129/2023-1.

Palavras Chave

Breast cancer during pregnancy; Placenta; miRNAs