Breast cancer is an aggressive disease with a high incidence in women worldwide. Two decades ago, a controversial hypothesis was proposed that cancer arises from a subpopulation of “tumor initiating cells” or “cancer stem cells-like” (CSC). Today, CSC are defined as small subset of somatic cancer cells within a tumor with self-renewal properties driven by the aberrant expression of genes involved in the maintenance of a stemness-like phenotype. The understanding of the underlying cellular and molecular mechanisms involved in the maintenance of CSC subpopulation are fundamental in the development and persistence of breast cancer. Nowadays, the hypothesis suggests that genetic and epigenetic alterations give rise to breast cancer stem cells (bCSC), which are responsible for self-renewal, tumor growth, chemoresistance, poor prognosis and low survival in patients. However, the prominence of bCSC, as well as the molecular mechanisms that regulates and promotes the malignant phenotypes, are still poorly understood. The role of non-coding RNAs (ncRNAs), such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) acting as oncogenes or tumor suppressor genes has been recently highlighted by a plethora of studies in breast cancer. These ncRNAs positively or negatively impact on different signaling pathways that govern the cancer hallmarks associated with bCSC, making them attractive targets for therapy. In this review, we present a current summary of the studies on the pivotal roles of lncRNAs and microRNAs in the regulation of genes associated to stemness of bCSC.

Lactose is a disaccharide of importance in humans dietary, food products, and the pharmaceutical industry. From the existing isomeric forms, -lactose is rarely found in nature. Thus, in this work, a simple methodology to obtain anhydrous -lactose ( L) from -lactose monohydrate ( L⋅H 2 O) is presented. The L⋅H 2 O powder was dispersed into a basic alcoholic solution (72 hours), at controlled conditions of temperature (27, 29, 31, and 32 ∘ C), without stirring. The slurry was dried at room temperature and characterized. Fourier transform infrared spectroscopy showed the formation of L for the samples prepared at 29 and 32 ∘ C. Raman spectroscopy confirmed this result and suggested the occurrence of crystalline L. Rietveld refinement of the X-ray diffraction patterns was employed to identify and quantify the composition of the isomers. The samples prepared at 29 and 31 ∘ C showed the formation of pure L, while those at 27 and 32 ∘ C showed the presence of L⋅H 2 O and a mixture of the two isomers, respectively. The morphology of the powders was studied by scanning electron microscopy, observing the formation of irregular shape L⋅H 2 O particles and axe-like L particles. Clearly, with this methodology, it was possible to obtain pure, crystalline, and anhydrous L at mild temperature.

Breast cancer is the most common cancer in women. Despite advances in diagnosis and prognosis, distal metastases occur in these patients in up to 15% of cases within 3 years of diagnosis. The main organs in which BC metastasises are the bones, lungs, liver, and brain. Unfortunately, 90% of metastatic patients will die, making this an incurable disease. Researchers are therefore seeking biomarkers for diagnosis and metastasis in different organs. Optimally, such biomarkers should be easy to detect using, preferably, non-invasive methods, such as using miRNA molecules, which are small molecules of about 22 nt that have as their main function the post-transcriptional regulation of genes. Furthermore, due to their uncomplicated detection and reproducibility in the laboratory, they are a tool of complementary interest for diagnosis, prognosis, and treatment. With this in mind, in this review, we focus on describing the most current studies that propose using miRNA independently as a potential biomarker for the diagnosis and prediction of brain, lung, liver, and bone metastases, as well as to open a window of opportunity to deepen this area of study to eventually use miRNAs molecules in clinical practice for the benefit of BC patients.

HOX transcript antisense RNA (HOTAIR) is an oncogenic long non-coding RNA frequently overexpressed in cancer. HOTAIR can enhance the malignant behavior of tumors by sponging microRNAs with tumor suppressor functions. Vasculogenic mimicry is a hypoxia-activated process in which tumor cells form three-dimensional (3D) channel-like networks, resembling endothelial blood vessels, to obtain nutrients. However, the role of HOTAIR in vasculogenic mimicry and the underlying mechanisms are unknown in human cancers. In the current study, we investigated the relevance of HOTAIR in hypoxia-induced vasculogenic mimicry in metastatic MDA-MB-231 and invasive Hs-578t triple negative breast cancer cells. Analysis of The Cancer Genome Atlas (TCGA) database using cBioPortal confirmed that HOTAIR was upregulated in clinical breast tumors relative to normal mammary tissues. Our quantitative RT-PCR assays showed a significant increase in HOTAIR levels after 48 h hypoxia relative to normoxia in breast cancer cell lines. Remarkably, knockdown of HOTAIR significantly abolished the hypoxia-induced vasculogenic mimicry which was accompanied by a reduction in the number of 3D channel-like networks and branch points. Likewise, HOTAIR silencing leads to reduced cell migration abilities of cancer cells. Bioinformatic analysis predicted that HOTAIR has a potential binding site for tumor suppressor miR-204. Luciferase reporter assays confirmed that HOTAIR is a competitive endogenous sponge of miR-204. Congruently, forced inhibition of HOTAIR in cells resulted in augmented miR-204 levels in breast cancer cells. Further bioinformatic analysis suggested that miR-204 can bind to the 3′ untranslated region of focal adhesion kinase 1 (FAK) transcript involved in cell migration. Western blot and luciferase reporter assays confirmed that FAK is a novel target of miR-204. Finally, silencing of HOTAIR resulted in low levels of cytoplasmic FAK protein and alterations in the organization of cellular cytoskeleton and focal adhesions. In summary, our results showed, for the first time, that HOTAIR mitigates cell migration and vasculogenic mimicry by targeting the miR-204/FAK axis in triple negative breast cancer cells.

Breast cancer is the most common type of cancer with the highest morbidity and mortality rates in women worldwide. Recent efforts to improve the current antitumor therapies have led to the development of novel treatment approaches based on the delivery of therapeutic non-coding RNAs (ncRNAs) using nanotechnology. Treatment methods using lipid-based nanoparticles (LBNPs) have greatly improved the delivery efficiency of ncRNAs into tumor cells and tissues. This type of delivery approach has provided significant advantages, such as reduced therapeutic doses, lower cytotoxicity to normal cells and the ability to reverse resistance to chemotherapy. LBNPs have demonstrated the ability to deliver therapeutic ncRNAs, more specifically microRNAs (miRNAs) and small interfering RNAs (siRNAs); this has been reported modulate the expression levels of oncogenes and tumor suppressor genes involved in several biological processes, including cell growth and proliferation, cell death, invasion and metastasis, thus impairing the malignant behavior of tumors. Therefore, ncRNA-based therapies combined with the LBNP delivery strategy, namely nanomiRNAs, may represent a promising antitumor strategy guaranteeing superior biocompatibility, higher biodegradability, lower immunogenicity and decreased toxicity to normal cells compared with other therapeutic approaches. The present review summarized the current knowledge of the application of LBNPs for delivering miRNAs and siRNAs in breast cancer cells and mouse models, in addition to discussing their promising antitumor effects. Contents1. Introduction 2. Lipid-based NPs (LBNPs) for non-coding RNA (ncRNA) delivery in breast cancer cells 3. Cationic liposomes 4. Neutral liposomes 5. Ionizable liposomes 6. Exosomes nanocarriers 7. Stealth liposomes 8. Triggered-release liposomes 9. Porphysomes 10. Lipid-coated calcium phosphate (LCP) NPs 11. Conclusions