Morales-González Sarai, Calaf Gloria M, Acuña Mónica, Tapia Julio C, Jara Lilian
Núcleo Interdisciplinario de Biología y Genética, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Independencia, Santiago 8380000, Chile.
Instituto de Alta Investigación, Universidad de Tarapacá, Arica 1010069, Chile.
Cells. 2025 Apr 18;14(8):612. doi: 10.3390/cells14080612.
Breast cancer (BC) is the most common malignant disease in women worldwide. Several studies have reported that microRNA-146a (miR-146a) dysregulation plays a role in multiple cancers, including BC. However, the mechanism underlying this association is controversial, possibly reflecting diverse roles for this miR in different types of cancer. The SNP rs2910164:G>C, located within the miR-146a precursor, has been linked to a BC risk. Our group previously showed a specific association between rs2910164:G>C and an increased BC risk in patients with early-onset sporadic BC. There are no studies in the literature that evaluate the functional consequences of the rs2910164 polymorphism in the BC process. Therefore, the goal of the present study was to evaluate in vitro the effect of the SNP rs2910164:G>C on BC progression in luminal A and triple-negative cell lines. We found that rs2910164:G>C upregulated the expression of two mature miR-146a sequences, 3p and 5p. Furthermore, pre-miR-146a-C enhanced proliferation, migration, and invasion in luminal A and triple-negative breast cells, as well as decreasing cisplatin-induced apoptosis. Interestingly, the pre-miR-146a C allele decreased cisplatin resistance in MCF-7 cells but increased cisplatin resistance in MDA-MB-231 cells. We propose that the rs2910164 C allele promotes miR-146a overexpression, which is causally involved in proliferation, migration, invasion, apoptosis, and cisplatin resistance.
乳腺癌（BC）是全球女性中最常见的恶性疾病。多项研究报告称，微小RNA-146a（miR-146a）失调在包括BC在内的多种癌症中发挥作用。然而，这种关联背后的机制存在争议，这可能反映了该miR在不同类型癌症中的多种作用。位于miR-146a前体中的单核苷酸多态性（SNP）rs2910164：G>C与BC风险相关。我们团队之前发现rs2910164：G>C与早发性散发性BC患者BC风险增加之间存在特定关联。文献中没有研究评估rs2910164多态性在BC过程中的功能后果。因此，本研究的目的是在体外评估SNP rs2910164：G>C对管腔A型和三阴性细胞系中BC进展的影响。我们发现rs2910164：G>C上调了两个成熟miR-146a序列3p和5p的表达。此外，前体miR-146a-C增强了管腔A型和三阴性乳腺细胞的增殖、迁移和侵袭能力，同时减少了顺铂诱导的细胞凋亡。有趣的是，前体miR-146a C等位基因降低了MCF-7细胞对顺铂的耐药性，但增加了MDA-MB-231细胞对顺铂的耐药性。我们认为，rs2910164 C等位基因促进miR-146a过表达，这与增殖、迁移、侵袭、细胞凋亡和顺铂耐药性存在因果关系。
