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PURPOSE: Breast cancer (BC) is one of the most common malignant tumors for women. The role and potential mechanisms of long non-coding RNA plasmacytoma variant translocation 1 (lncRNA PVT1) were explored in BC cell migration and invasion. METHODS: PVT1, miR-148a-3p and Rhoassociated, coiledcoil containing protein kinase 1 (ROCK1) mRNA expressions were detected using real-time fluorescent quantitative polymerase chain reaction (qRT-PCR). The ROCK1 protein expression was detected by Western blotting. The relationship of PVT1, miR-148a-3p and ROCK1 was analyzed by Dual Luciferase activity, RNA immunoprecipitation (RIP) and Spearman correlation analysis. Cell invasion and migration were detected by Transwell assay. RESULTS: Upregulation of PVT1 and ROCK1, and downregulation of miR-148a-3p were observed in BC tissues and cell lines. According to the analysis of Dual Luciferase activity, RIP and Spearman correlation analysis, miR-148a-3p directly binds to PVT1, and ROCK1 is a target of miR-148a-3p. In addition, PVT1 regulated the cells migration and invasion by regulating miR-148a-3p and ROCK1 expression. CONCLUSION: These data demonstrated that PVT1 was upregulated and facilitated to the cell migration and invasion of BC by the regulation of miR-148a-3p and ROCK1, indicating that PVT1 may be a potential biomarker of BC diagnosis and treatment.
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Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante/genética , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Luciferases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Quinases Associadas a rho/genética , Quinases Associadas a rho/metabolismoRESUMO
PURPOSE: To investigate the effect of microRNA-543 (miR-543) on the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of triple-negative breast cancer (TNBC) cells, and the associated mechanism. METHODS: Human breast cancer cells (MDA-MB-231, HCC1937, and MCF-7, ZR-75-1) and normal human breast epithelial cell line (MCF10A) were transfected with miR-543 mimics or inhibitor using lipofectamine 2000. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting were used to determine the mRNA and protein expression levels of miR-543, actin-like protein 6A (ACTL6A), vimentin, Snail, and E-cadherin in breast cancer cells/tissue. Cell counting kit-8 (CCK-8), wound-healing, and Transwell assays were used to measure the effect of miR-543 on TNBC cell proliferation, invasion, and migration. Overall survival was determined using data from Gene Expression Omnibus (GEO) and Cancer Genome Atlas (TCGA) databases. Bioinformatics analysis and luciferase reporter gene assay were used to determine the regulatory effect of miR-543 on ACTL6A. RESULTS: The level of expression of miR-543 was significantly lower in breast cancer cells/tissue than in normal human breast epithelial cell/tissue (p < 0.05). MicroRNA-543 expression level was significantly reduced in TNBC cells/tissue, relative to the other breast cancer cells/normal breast tissue (p < 0.05). MicroRNA-543 significantly suppressed tumor growth and the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of TNBC cells, in mouse xenograft model (p < 0.05). CONCLUSIONS: miR-543 influences the biological behavior of TNBC cells by directly targeting ACTL6A gene. miR-543 could serve as a novel diagnostic and therapeutic target for TNBC.
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Actinas/fisiologia , Movimento Celular , Proliferação de Células , Proteínas Cromossômicas não Histona/fisiologia , Proteínas de Ligação a DNA/fisiologia , Regulação para Baixo , Transição Epitelial-Mesenquimal , MicroRNAs/fisiologia , Neoplasias de Mama Triplo Negativas/patologia , Animais , Humanos , Camundongos , Invasividade Neoplásica , Células Tumorais CultivadasRESUMO
Geese (Anser cygnoides) possess stronger ability of roughage digestion and utilization than other poultries, hence, it has become the focus of attention of scientists. Duodenal, jejunum and ileum were mainly participated in food digestion and nutrient absorption, while the cecum was responsible for biological fermentation. Effects on the geese's cecal microbiota community by feeding with the all-grass diet have been investigated, however, whether it had an influence on the geese's duodenal microbiota community remains unexplored. To address this problem, geese feeding with the basal diet for 28 days (G1), the basal diet for 28 days and the all-grass diet for the following 14 days (G2), the basal diet for 42 days (G3) were selected, respectively. The duodenal segments of geese were collected and the hypervariable V3-V4 region of the bacterial 16S rRNA gene was sequencing. A total of 4 main phyla and 16 main genera were identified. Moreover, we also successfully identified that two taxa including the Helcococcus and Clostridium could be used as distinguishing biomarkers specific to G2. The functional profiles of the duodenum microbiota were mainly involved in the membrane transport (e.g. ABC transporters), amino acid metabolism, energy metabolism, metabolism of cofactors and vitamins, and cellular processes and signaling pathways in geese feeding with the all-grass diet. In conclusion, the all-grass diet could impact the composition of duodenal microbiota. However, to resolve the underlying mechanism of the fiber digesting and utilization in geese's gut microbiota, the whole intestinal system needs to be assessed by further studies.(AU)
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Animais , Microbiota , Microbioma Gastrointestinal , Gansos/fisiologia , Ração Animal , Ingestão de Alimentos/fisiologiaRESUMO
Exosomes, the nanoscale phospholipid bilayer vesicles, enriched in selected proteins, nucleic acids and lipids, which they participated in a variety of biological processes in the body, including physiology and pathology. CircRNAs (circular RNAs) are a class of single-stranded closed molecules with tissue development specific expression patterns that have crucial regulatory functions in various diseases. Non-coding RNAs (such as microRNAs and long noncoding RNAs) in exosomes have also been shown to play an important regulatory role in humans. However, little research has focused on exosomal circRNAs. Recently, CircRNAs have been identified to be enriched and stably expressed in exosomes. In this review, we summarize the biogenesis and biological functions of exosomes and circRNA, and further revealed the potential role of exosome-derived circRNA in different diseases. Besides, we propose its use as a diagnostic marker and therapeutic punctuation for diseases, especially in cancer.
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Doença/genética , Exossomos , Neoplasias/genética , RNA Circular/fisiologia , HumanosRESUMO
Innate immune cells can develop exacerbated immunologic response and long-term inflammatory phenotype following brief exposure to endogenous or exogenous insults, which leads to an altered response towards a second challenge after the return to a nonactivated state. This phenomenon is known as trained immunity (TI). TI is not only important for host defense and vaccine response but also for chronic inflammations such as cardiovascular and metabolic diseases such as atherosclerosis. TI can occur in innate immune cells such as monocytes/macrophages, natural killer cells, endothelial cells (ECs), and nonimmune cells, such as fibroblast. In this brief review, we analyze the significance of TI in ECs, which are also considered as innate immune cells in addition to macrophages. TI can be induced by a variety of stimuli, including lipopolysaccharides, BCG (bacillus Calmette-Guerin), and oxLDL (oxidized low-density lipoprotein), which are defined as risk factors for cardiovascular and metabolic diseases. Furthermore, TI in ECs is functional for inflammation effectiveness and transition to chronic inflammation. Rewiring of cellular metabolism of the trained cells takes place during induction of TI, including increased glycolysis, glutaminolysis, increased accumulation of tricarboxylic acid cycle metabolites and acetyl-coenzyme A production, as well as increased mevalonate synthesis. Subsequently, this leads to epigenetic remodeling, resulting in important changes in chromatin architecture that enables increased gene transcription and enhanced proinflammatory immune response. However, TI pathways and inflammatory pathways are separated to ensure memory stays when inflammation undergoes resolution. Additionally, reactive oxygen species play context-dependent roles in TI. Therefore, TI plays significant roles in EC and macrophage pathology and chronic inflammation. However, further characterization of TI in ECs and macrophages would provide novel insights into cardiovascular disease pathogenesis and new therapeutic targets. Graphic Abstract: A graphic abstract is available for this article.
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Células Endoteliais/imunologia , Macrófagos/imunologia , Animais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/imunologia , Citocinas/biossíntese , Metabolismo Energético , Epigênese Genética , Humanos , Imunidade Inata , Memória Imunológica , Infecções/etiologia , Infecções/imunologia , Inflamação/etiologia , Inflamação/imunologia , Doenças Metabólicas/etiologia , Doenças Metabólicas/imunologia , Redes e Vias Metabólicas/imunologia , Modelos Imunológicos , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/imunologia , Fatores de RiscoRESUMO
ABSTRACT Objective: To analyse the incidence of long and short corrected QT (QTc) in a healthy sample of the population of Changsha in China. Methods: Standard 12-lead electrocardiograms (ECGs) were performed on 4025 subjects in Changsha of China, whose age ranged from 6 minutes after birth to 83 years, between January 1993 and December 2012. Heart rate and QT interval were measured and recorded. Corrected QT was calculated with Bazett´s formula (QTc = QT/RR0.5). All recruited individuals had taken healthy examination, ruling out general health issue, in The Second Xiangya Hospital of Central South University. Statistical analyses were performed using the SPSS 16.0 software (IBM Corp, Armonk, NY, USA). Results: The incidence of short QTc was 7.13% (287/4025 cases). The peak values of the incidence were in the 30-40 years group (15.71%). The low values were in the 1-3 months group and 3-6 months group (0%, 0.76%), respectively. The incidence of long QTc was 3.16% (127/4025 cases). The values diminished significantly after adulthood. The low values were in the age groups of 18-30 years (0.86%) and 30-40 years (0.71%), respectively. After the age of 50 years, the incidence of long QTc increased with age 50-60 years and 60-70 years and 70-83 years (7.89%, 9.06%, 14.06%), respectively. There was no statistically significant difference between the genders (p > 0.05). Conclusion: The peak incidences of long and short QTc existed in two separate age groups in the healthy sample. The peak incidence of short QTc was in the age group of 18-40 years, and the peak incidence of long QTc was in the age group beyond the 50 years. For these two age groups, it was recommended to pay close attention to the changes in their QTc in order to prevent cardiovascular events.
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OBJECTIVE: Chronic inflammation is recognized as a risk factor for colorectal cancer (CRC) development. Baicalin (BI), a major constituent in an anti-inflammatory herb Scutellaria baicalensis, can be biotransformed into baicalein (BE) by the intestinal microbiota. We evaluated the anti-inflammation and anti-CRC effects of the metabolite BE. METHODS: The in vitro biotransformation by human intestinal microbiota from BI into BE has been determined with HPLC. Using a gut-specific ApcMin/+ mouse model, the effects of oral BE on the life span, organ index, and tumor multiplicity were evaluated. The expressions of inflammatory cytokines were determined using ELISA. To verify the in vivo data, the anti-inflammatory and antiproliferative effects of BE were determined with an in vitro cell model. RESULTS: HPLC analysis showed that BI was quickly transformed into BE by the intestinal microbiota. Oral BE (30 mg/kg/day) significantly increased the life span, from 125.2 to 218.4 days (P < 0.01%). BE treatment also decreased intestine index and increased spleen index. Compared with the model group, following BE treatment, tumor numbers were significantly reduced in the small intestine and colon (P < 0.01, P < 0.05, respectively). In the gut tissues, BE treatment significantly reduced inflammatory cytokine levels such as IL-1ß, IL-2, IL-6, IL-10, G-CSF, and GM-CSF. In vitro data supported our in vivo results that the anti-CRC effects of BE were via the inhibition of gut inflammation and induction of cancer cell death. CONCLUSION: Our results suggest that the parent compound BI can be quickly converted into its microbial metabolite BE, which has stronger bioactive effects than BI. Baicalein is an active chemopreventive metabolite for inflammatory associated CRC.
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Antioxidantes/farmacologia , Colo/efeitos dos fármacos , Neoplasias Colorretais/patologia , Citocinas/efeitos dos fármacos , Flavanonas/farmacologia , Intestino Delgado/efeitos dos fármacos , Proteína da Polipose Adenomatosa do Colo/genética , Animais , Colo/imunologia , Colo/patologia , Neoplasias Colorretais/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Flavanonas/metabolismo , Flavonoides/metabolismo , Microbioma Gastrointestinal , Células HT29 , Humanos , Inflamação/metabolismo , Neoplasias Intestinais/genética , Neoplasias Intestinais/patologia , Intestino Delgado/imunologia , Intestino Delgado/patologia , Longevidade , Camundongos , Carga TumoralRESUMO
BACKGROUND: The prognostic and clinical significance of single hormone receptor expression in breast cancer has not been clearly established. The goal of this study was to conduct a meta-analysis to compare the clinical outcomes of patients with ER+PR- tumours and ER-PR+ tumours to those of patients with ER+PR+ tumours. METHODS: A systematic review of the literature was conducted to identify studies that compared the clinical outcome of patients with ER+PR- tumours or ER-PR+ tumours with those of patients with ER+PR+ tumours. A total of 18 studies met the inclusion criteria and included 217,485 women. Standard methods for meta-analysis were used, including fixed-effect models. RESULTS: Patients with ER+PR- tumours or ER-PR+ tumours had significantly worse DFS (HR 1.60, 95% CI 1.44-1.77 and HR 2.27, 95% CI 1.67-3.09), BCSS (HR 1.43, 95% CI 1.33-1.53 and HR 1.82, 95% CI 1.68-1.98) and OS (HR 1.38, 95% CI 1.28-1.47 and HR 1.48, 95% CI 1.17-1.89) than those of patients with ER+PR+ tumours. In subgroup analyses, patients who had ER+PR- tumours experienced a higher risk of recurrence than patients with ER+PR+ tumours in the HER2- (HR 1.57, 95% CI 1.32-1.87), LN - (HR 2.07, 95% CI 1.44-2.86) and endocrine therapy (HR 1.65, 95% CI 1.45-1.89) subgroup. Patients who had HER2- and ER-PR+ tumours had an increased risk of recurrence compared with patients who had HER2- and ER+PR+ tumours (HR 3.10, 95% CI 1.92-5.10). CONCLUSIONS: Among patients with hormone receptor-positive breast cancer, patients with either ER+PR- tumours or ER-PR+ tumours have a higher risk of recurrence and a shorter survival time than those with ER+PR+ tumours. Patients with both types of breast cancer need additional or better treatments.
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Neoplasias da Mama/mortalidade , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Neoplasias da Mama/química , Feminino , Humanos , Recidiva Local de Neoplasia/etiologia , Receptor ErbB-2/análiseRESUMO
OBJECTIVE: Hyperhomocysteinemia (HHcy) is a potent risk factor for diabetic cardiovascular diseases. We have previously reported that hyperhomocysteinemia potentiates type 1 diabetes mellitus-induced inflammatory monocyte differentiation, vascular dysfunction, and atherosclerosis. However, the effects of hyperhomocysteinemia on vascular inflammation in type 2 diabetes mellitus (T2DM) and the underlying mechanism are unknown. Approach and Results: Here, we demonstrate that hyperhomocysteinemia was induced by a high methionine diet in control mice (homocysteine 129 µmol/L), which was further worsened in T2DM db/db mice (homocysteine 180 µmol/L) with aggravated insulin intolerance. Hyperhomocysteinemia potentiated T2DM-induced mononuclear cell, monocyte, inflammatory monocyte (CD11b+Ly6C+), and M1 macrophage differentiation in periphery and aorta, which were rescued by folic acid-based homocysteine-lowering therapy. Moreover, hyperhomocysteinemia exacerbated T2DM-impaired endothelial-dependent aortic relaxation to acetylcholine. Finally, transfusion of bone marrow cells depleted for Ly6C by Ly6c shRNA transduction improved insulin intolerance and endothelial-dependent aortic relaxation in hyperhomocysteinemia+T2DM mice. CONCLUSIONS: Hyperhomocysteinemia potentiated systemic and vessel wall inflammation and vascular dysfunction partially via inflammatory monocyte subset induction in T2DM. Inflammatory monocyte may be a novel therapeutic target for insulin resistance, inflammation, and cardiovascular complications in hyperhomocysteinemia+T2DM.
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Antígenos Ly/genética , Aterosclerose/complicações , Diabetes Mellitus Tipo 2/genética , Hiper-Homocisteinemia/complicações , Monócitos/metabolismo , Doenças Vasculares/etiologia , Animais , Diferenciação Celular/genética , Modelos Animais de Doenças , Endotélio Vascular/metabolismo , Feminino , Hiper-Homocisteinemia/genética , Insulina/uso terapêutico , Resistência à Insulina , Macrófagos/metabolismo , Camundongos , Distribuição Aleatória , Fatores de Risco , Sensibilidade e Especificidade , Doenças Vasculares/fisiopatologiaRESUMO
PURPOSE: The prognostic value of nonsentinel lymph-node (NSLN) status in breast cancer remains unclear. This study was designed to investigate the prognostic value of NSLN status in SLN-positive breast cancer. METHODS: Retrospective 873 consecutive primary breast cancer patients from a single institution who were SLN-positive and underwent axillary lymph-node dissection (ALND) were included. Patients with incomplete clinical information or loss of follow-up were excluded. Survival analysis in patients with the same number of positive LNs and patients belonging to the same American Joint Committee on Cancer (AJCC) node (N) classification was performed to establish a proposal for incorporating the NSLN status into the breast cancer staging system. RESULTS: The median follow-up was 41 months. Positive NSLN status was a significantly unfavorable factor for recurrence-free survival (RFS) (HR: 4.31, P < 0.001) and distant recurrence-free survival (DRFS) (HR: 3.62, P < 0.001). The survival of patients with one positive SLN and one positive NSLN (N = 97) was significantly worse than that of patients with two positive SLNs (N = 68; RFS, P = 0.011; DRFS, P = 0.027). Positive NSLN status was a significantly unfavorable factor affecting survival in patients with the AJCC N1 classification (N = 806; RFS, HR: 2.85, P = 0.002; DRFS, HR: 2.81, P = 0.004). No significant difference in survival was found between LN-negative (N = 361) and NSLN-negative AJCC N1 classification (N = 363) patients. CONCLUSIONS: Positive NSLN status has an independent prognostic value in breast cancer patients with 1-3 positive LNs, and the NSLN status should be incorporated into the breast cancer staging system.