Breast cancer (BC) is the most common cancer in women worldwide. This highly heterogeneous disease is molecularly stratified into luminal A, luminal B, HER2, triple-negative/basal-like, and normal-like subtypes. An important aspect in BC progression is the activation of inflammatory processes. The activation of CD8+/Th1, NK, and M1 tumor associated macrophages (TAMs), leads to tumor destruction. In contrast, an anti-inflammatory response mediated by CD4+/Th2 and M2 TAMs will favor tumor progression. Inflammation also stimulates the production of inflammatory mediators like reactive oxygen species (ROS). In chronic inflammation, ROS activates oxidative stress and endothelial dysfunction. In cancer, ROS plays a dual role with anti-tumorigenic and pro-tumorigenic effects in cell signaling pathways that control proliferation, survival, apoptosis, and inflammation. MicroRNAs (miRNAs), which are known to be involved in BC progression and inflammation, can be regulated by ROS. At the same time, miRNAs regulate the expression of genes modulating oxidative stress. In this review, we will discuss the interplay between inflammation, ROS, and miRNAs as anticancer and tumor promoter molecules in BC. A clear understanding of the role of miRNAs in the regulation of ROS production and inflammation, may lead to new opportunities for therapy in BC.

Background: Breast cancer (BC) is the most diagnosed cancer in women worldwide. MicroRNAs (miRNAs) are involved in different processes of BC and their deregulation can cause them to act as oncogenes or tumor suppressors, participating in cancer progression or also as therapeutic target. Using The Cancer Genome Atlas (TCGA) database, we found that miR-660-5p is significantly overexpressed and associated with poor survival in patients with this pathology. Moreover, it is reported that miR-660-5p can induce BC progression through transcription factor CP2 (TFCP2) and the down regulation of tet-eleven translocation 2 (TET2). In this project, we propose to identify the role of miR-660-5p in proliferation, migration, invasion, angiogenesis, and possible targets involved in these processes in BC cell lines. Methods: Basal levels of miR-660-5p were determined in BC cells MDA-MB-231 and MCF-7, and in human epithelial breast cells MCF-10A by RT-qPCR. The effect of miR-660-5p was evaluated on proliferation, migration, and invasion processes using MDA-MB-231 and MCF-7 cells. HUVEC cells were used to assess angiogenesis. All cell lines were transfected with miR-660-5p inhibitor. Analysis of nine miRNA-target prediction databases was made to identify targets of miR-660-5p. We selected the target genes predicted by at least three of these programs, and their expression was evaluated by RT-qPCR in a customized 384-well plate. Results: We found that miR-660-5p is significantly upregulated in MDA-MB-231 and MCF-7, compared to MCF-10A cells. In addition, we observed a significant decrease in proliferation, migration, and invasion of BC cells transfected with miR-660-5p inhibitor, compared to non-treated cells and miRNA inhibitor negative control treated cells. Similarly, we observed a significant decrease in angiogenesis of HUVEC cells transfected with miR-660-5p inhibitor. Furthermore, of all the miR-660-5p targets identified by prediction databases 21 were selected, and of these, 7 were observed upregulated and 1 downregulated. Conclusions: The results show that miR-660-5p is upregulated and involved in proliferation, migration, invasion, and angiogenesis of BC, which may lead us to suggest that this miRNA act as an onco-miRNA. In addition, seven potential miR-660-5p target genes were identified, but further validation assays are needed to clarify their implication in this disease. Citation Format: Valeria Villarreal-García, José Roberto Estupiñan Jimenez, Ricardo Noriega, Recep Bayraktar, Diana Reséndez-Pérez, Cristina Rodríguez-Padilla, José Manuel Vázquez-Guillén, Gabriel Lopez-Berestein, Pablo E. Vivas-Mejía, Vianey Gonzalez-Villasana. Effect of miR-660-5p in breast cancer progression [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-22-03.

Background: MiRNAs are non-coding RNA molecules and its function is the regulation of gene expression. In cancer, the deregulation of miRNAs allows them to act as oncogenes or tumor suppressors. From an analysis of the expression of miRNAs in breast cancer (BC) in The Cancer Genome Atlas (TCGA), it was identified that miR-1307-3p is significantly overexpressed in the tumor tissue compared to healthy tissue from patients. So far, in BC, it has only been reported that this miRNA inhibits SMYD4 and that it is involved in resistance to cisplatin through its effect on Mdm4. In this project we propose to identify the role of miR-1307-3p in proliferation, migration, invasion, angiogenesis, and possible targets involved in these processes in BC cells. Methods: RT-qPCR was used to evaluate basal levels of miR-1307-3p in the BC cell lines MDA-MB-231 and MCF-7, and the human epithelial breast MCF-10A cells. Later, we determined the effect of miR-1307-3p on proliferation, migration, and invasion in MDA-MB-231 and MCF-7, and angiogenesis in the HUVEC endothelial cells. All assays were carried out using the miR-1307-3p inhibitor. Finally, nine miRNA-target prediction databases were analyzed to identify potential miR-1307-3p target genes, and their expression was analyzed by RT-qPCR in a designed 384-well plate. Results: We found that miR-1307-3p is overexpressed in MDA-MB-231 and MCF-7, compared to MCF-10A cells. We also identified that transfection with the miR-1307-3p inhibitor causes a significant decrease in the processes of proliferation, migration, invasion, and angiogenesis, when compared with untreated or negative control transfected cells. For its part, prediction databases analysis allowed us to identify 19 potential targets of miR-1307-3p. Finally, by RT-qPCR, the overexpression of 3 and the downregulation of 2 genes were confirmed. Conclusions: MiR-1307-3p is overexpressed in BC cells. Furthermore, miR-1307-3p induces the processes of proliferation, migration and invasion in BC cells, and angiogenesis in HUVEC cells. These observations suggest that miR-1307-3p can acts as an onco-miRNA. In addition, the expression of 5 of the predicted target genes were altered by miR-1307-3p inhibitor. Further analysis to validate the implication of this miR-1307-3p targets are needed to understand its importance in BC. Citation Format: José Roberto Estupiñan Jimenez, Valeria Villarreal-García, Ricardo Noriega, Recep Bayraktar, Diana Reséndez-Pérez, Cristina Rodríguez-Padilla, José Manuel Vázquez-Guillén, Fermín Mar-Aguilar, Gabriel Lopez-Berestein, Pablo E. Vivas-Mejía, Vianey Gonzalez-Villasana. Functional effect of miR-1307-3p on breast cancer progression [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-22-04.