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Breast cancer (BC) is one of the leading causes of death in women worldwide. A major challenge in BC is chemoresistance, which is often modulated by epigenetic regulators such as long non-coding RNAs (lncRNAs). Because these regulator lncRNAs may play diverse roles, determining their specific pathways and/or functions is crucial to identify possible biomarkers and/or therapeutic targets for BC. In this study, we used gene expression microarrays in order to identify lncRNAs related to the BC biology. We found, among six differentially expressed (DE) lncRNAs, that the expression of lnc-ERP44-3:6 was consistently down-regulated in all breast tumor tissues compared to normal adjacent tissues of BC patients from northeastern Mexico. Since the role of lnc-ERP44-3:6 remains unknown in BC, we induced its transient overexpression in three different BC cell lines (i.e., MCF10A, MCF-7, and HCC1395) by transfection in order to elucidate its potential downstream effects. Remarkably, our results showed a significant increase in cell death and chemosensitivity to cisplatin at 48 h post-transfection (p < 0.01). In addition, we observed that GAPDH and FAS were up-regulated following the overexpression of lnc-ERP44-3:6. As GAPDH and FAS promote apoptosis in cancer, our findings suggest that the lnc-ERP44-3:6 overexpression induces cell death possibly via up-regulation of one or both genes in BC cell lines. To the best of our knowledge, this is the first study evaluating the overexpression of lnc-ERP44-3:6 and providing insights about its role in BC cells, which suggests that this lncRNA may be an interesting candidate as a potential therapeutic target for BC in our population. However, further studies would be needed to clarify the mechanisms by which an overexpression of lnc-ERP44-3:6 causes both cell death and chemosensitivity to cisplatin. [ABSTRACT FROM AUTHOR]

The mammary glands are made of different cell populations that have great cellular plasticity, which is mainly regulated by epigenetic changes that allow the expression of specific transcripts needed depending on the stage of development (embryonic, puberty, pregnancy, lactation, involution, and postmenopause). Therefore, it is important to maintain strict regulation at each stage because aberrations in epigenetic regulation can lead to breast cancer. Among the epigenetic regulators are long non-coding RNAs (lncRNAs), which play important roles during the development of the breasts. Further, they can be used as biomarkers in breast cancer since their expression and emergence correlate with the patient's survival, as well as the aggressiveness of the tumor; the lncRNAs lead to epigenetic changes and the activation of signaling pathways, causing an accelerated rate of proliferation, metastasis, and evasion of the action of chemotherapeutic agents. Therefore, lncRNAs may be potential therapeutic targets. In this review, we show examples of lncRNAs that exert resistance on the different subtypes of breast cancer, through the activation of signaling pathways protein kinase b (AKT), the extracellular signal-regulated kinases (ERK), the mammalian target of rapamycin (mTOR), and (wingless/integrated [Wnt])/(beta-catenin). Some of these pathways are shared among the different subtypes, allowing cancer cells to activate the same pathways through different mechanisms, promoting tumor growth and resistance to various therapeutic agents. Furthermore, the mechanisms by which lncRNAs help acquire resistance and strategies to determine their function are presented in this review. [ABSTRACT FROM AUTHOR]