MicroRNA-506 ameliorates breast cancer-induced osteolytic bone metastasis via the NFATc-1 signaling pathway.

Breast cancer is becoming a common life-threatening disease, especially in women, along with higher incidence and mortality. MicroRNA (miR)-506 was reported to participate in breast cancer progression, while the role of miR-506 in breast cancer-induced osteolytic bone metastasis is unclear. In the present study, we found significant downregulation of miR-506 in breast cancer tissues and cell lines. Overexpression of miR-506 notably reduced the proliferative, migratory and invasive rates of MCF7 and MDA-MB-231 cells, and reduced the production of inflammatory factors IL-6 and TNF-α in MCF7 cells. Moreover, overexpression of miR-506 obviously inhibited tumor growth in an in vivo animal model. In addition, overexpression of miR-560 efficiently attenuated breast cancer-induced osteolysis in vivo, which was characterized by increased bone volume/total volume (BT/TV), trabecular number (Tb. N), and trabecular thickness (Tb. Th), as well as the reduced trabecular separation (Tb. Sp). The nuclear factor of activated T cell cytoplasmic 1 (NFATc1) was identified as a downstream target of miR-506, and overexpression of miR-506 could inhibit breast cancer progression by targeting NFATc1. Furthermore, our results showed that NFATc-1 might participate in the inhibition of miR-506 on breast cancer-induced osteolysis. In conclusion, our findings provide insights into understanding the pathogenesis of breast cancer and breast cancer-induced osteolytic bone metastasis, and miR-506 might serve as a novel biomarker for this disease.

MCP-1 stimulates MMP-9 expression via ERK 1/2 and p38 MAPK signaling pathways in human aortic smooth muscle cells.

OBJECTIVE: We investigated the molecular mechanism underlying the role of monocyte chemoattractant protein-1 (MCP-1) in the formation and development of human abdominal aortic aneurysm (AAA). METHODS: We examined protein expression profiles using a protein array and found that MCP-1 was the most highly expressed protein in AAA tissues compared with normal aortas. To investigate the potential mechanism of MCP-1 involvement in the pathogenesis of AAA, we treated human aortic smooth muscle cells (HASMCs) with human recombinant MCP-1. RESULTS: MCP-1 was the most highly expressed protein in AAA tissues compared with normal aorta; matrix metalloproteinase-9 (MMP-9) expression was also significantly increased. Treatment with MCP-1 significantly increased the expression and activation of MMP-9 and activated the three major mitogen activated protein kinases (MAPKs) extracellular signal regulated kinase (ERK), c-Jun amino terminal kinase (JNK1/2) and p38 MAPK. Furthermore, MCP-1-induced secretion of MMP-9 was inhibited by U0126 (inhibitor of the ERK 1/2 pathway) and SB203580 (inhibitor of the p38 MAPK pathway), but not SP600125 (inhibitor of the JNK1/2 pathway). CONCLUSION: These data demonstrate that MCP-1 stimulates secretion of MMP-9 directly through the ERK1/2 and p38 MAPK mediated pathways in HASMCs. Thus, inhibition of this molecular mechanism might be a potential therapeutic target in the non-surgical treatment of AAA.

Advances in Single-Cell Transcriptome Sequencing and Spatial Transcriptome Sequencing in Plants.

"Omics" typically involves exploration of the structure and function of the entire composition of a biological system at a specific level using high-throughput analytical methods to probe and analyze large amounts of data, including genomics, transcriptomics, proteomics, and metabolomics, among other types. Genomics characterizes and quantifies all genes of an organism collectively, studying their interrelationships and their impacts on the organism. However, conventional transcriptomic sequencing techniques target population cells, and their results only reflect the average expression levels of genes in population cells, as they are unable to reveal the gene expression heterogeneity and spatial heterogeneity among individual cells, thus masking the expression specificity between different cells. Single-cell transcriptomic sequencing and spatial transcriptomic sequencing techniques analyze the transcriptome of individual cells in plant or animal tissues, enabling the understanding of each cell's metabolites and expressed genes. Consequently, statistical analysis of the corresponding tissues can be performed, with the purpose of achieving cell classification, evolutionary growth, and physiological and pathological analyses. This article provides an overview of the research progress in plant single-cell and spatial transcriptomics, as well as their applications and challenges in plants. Furthermore, prospects for the development of single-cell and spatial transcriptomics are proposed.

Overview of molecular mechanisms of plant leaf development: a systematic review.

Leaf growth initiates in the peripheral region of the meristem at the apex of the stem, eventually forming flat structures. Leaves are pivotal organs in plants, serving as the primary sites for photosynthesis, respiration, and transpiration. Their development is intricately governed by complex regulatory networks. Leaf development encompasses five processes: the leaf primordium initiation, the leaf polarity establishment, leaf size expansion, shaping of leaf, and leaf senescence. The leaf primordia starts from the side of the growth cone at the apex of the stem. Under the precise regulation of a series of genes, the leaf primordia establishes adaxial-abaxial axes, proximal-distal axes and medio-lateral axes polarity, guides the primordia cells to divide and differentiate in a specific direction, and finally develops into leaves of a certain shape and size. Leaf senescence is a kind of programmed cell death that occurs in plants, and as it is the last stage of leaf development. Each of these processes is meticulously coordinated through the intricate interplay among transcriptional regulatory factors, microRNAs, and plant hormones. This review is dedicated to examining the regulatory influences of major regulatory factors and plant hormones on these five developmental aspects of leaves.

MicroRNA-337-3p impedes breast cancer progression by targeting cyclin-dependent kinase 1.

MicroRNAs (miRNAs/miRs) function as key regulators in breast cancer (BC). The present study aimed to verify the function and molecular regulation of miR-337-3p in BC cells. Bioinformatics analysis was performed to screen key genes and miRNAs associated with BC. Reverse transcription-quantitative PCR and western blot analyses were performed to detect RNA and protein expression levels. Cell Counting Kit-8, BrdU and cell adhesion assays, and flow cytometric analysis were performed to assess the biological behaviors of BC cells. The dual-luciferase reporter, RNA pull-down assays, and Pearson's correlation analysis were performed to determine the association between miRNAs and mRNAs. Bioinformatics analysis revealed that miR-337-3p and cyclin-dependent kinase 1 (CDK1) acted as key regulators in BC. In addition, miR-337-3p was expressed at low levels in BC cells and tissues, which suppressed BC progression. CDK1 expression was upregulated in BC cells and tissues, which was associated with increased cell proliferation and adhesion, as well as decreased apoptosis in BC. Notably, miR-337-3p targeted CDK1 to inhibit BC cell progression. Taken together, the results of the present study suggest that miR-337-3p plays a tumor-suppressive role in BC by targeting CDK1.

Metabolic Variation Dictates Cardiac Pathogenesis in Patients With Tetralogy of Fallot.

BACKGROUND: Herein, we aimed to analyze cardiac metabolic reprogramming in patients with tetralogy of Fallot (ToF). METHODS: Cardiac metabolic reprogramming was analyzed through comprehensive bioinformatics analysis, which included gene set enrichment, gene set variation, and consensus clustering analyses, so as to assess changes in metabolic pathways. In addition, full-spectrum metabolomics analysis was performed using right atrial biopsy samples obtained from patients with ToF and atrial septal defect (ASD) before cardiopulmonary bypass; ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to construct a metabolic map of cardiac metabolic reprogramming in cyanotic congenital heart disease. RESULTS: The metabolic maps of carbohydrate metabolic process and heme metabolism were significantly activated, while bile acid metabolism, lipid droplet, and lipid binding were primarily restrained in ToF samples as compared with that in ASD samples. The reprogramming of butanoate metabolism was identified basing on the UPLC-MS/MS detection and analysis in myocardial hypoxia damage in cyanotic heart disease. Finally, the butanoate metabolism-related hub regulators ALDH5A1 and EHHADH were identified and they were significantly downregulated in ToF samples. CONCLUSIONS: The metabolic network of butanoate metabolism involved ALDH5A1 and EHHADH, which could contribute to myocardial tissue damage in cyanotic congenital heart of ToF. Our results provide further insights into the mechanisms underlying metabolic reprogramming in cyanotic congenital heart disease and could lead to the identification of potential therapeutic targets.