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OBJECTIVE: MicroRNAs have been reported to play an important role in the invasion and metastasis of cervical cancer. miR-183 was found to inhibit or promote the invasion and metastasis of multiple solid tumors. However, the roles of miR-183 in cervical cancer are unclear. METHODS: In this study, miR-183 expression levels were measured in 53 cervical cancer and 13 normal cervical tissues by qRT-PCR. The effects of forced expression of miR-183 on cervical cancer cells invasion and metastasis were investigated using Transwell uncoated or coated with growth factor-reduced Matrigel for migration or invasion assays, respectively. RESULTS: We found that miR-183 expression levels were significantly down-regulated in cervical cancer tissues compared with normal tissues (0.15±0.011 to 0.86±0.049). Ectopic expression of miR-183 resulted in the suppression of invasion and migration of cervical cancer cell lines, siha and Hela cells (p<0.0001). Bioinformatics analysis revealed that MMP-9 was the potential target of miR-183 and it was found that MMP-9 was remarkably up-regulated in cervical cancer. Furthermore, a dual-luciferase reporter assay showed that MMP-9 as a target of miR-183 (p<0.0001). The invasion and metastasis ability of siha and Hela was suppressed when MMP-9 was down-regulated in vitro (p<0.0001). CONCLUSIONS: In conclusion, our study revealed that miR-183 might be a tumor suppressor via inhibiting the invasion and metastasis of cervical cancer cells through targeting MMP-9, indicating that miR-183 may be a novel potential therapeutic target for cervical cancer.
Asunto(s)
Genes Supresores de Tumor/fisiología , Metaloproteinasa 9 de la Matriz/genética , MicroARNs/fisiología , Neoplasias del Cuello Uterino/patología , Línea Celular Tumoral , Movimiento Celular , Biología Computacional , Femenino , Humanos , Metaloproteinasa 9 de la Matriz/análisis , MicroARNs/análisis , Invasividad Neoplásica , Metástasis de la Neoplasia , Neoplasias del Cuello Uterino/mortalidadRESUMEN
[This corrects the article DOI: 10.3389/fnut.2022.933193.].
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This study aimed to investigate the impact of probiotic fermentation on the active components and functions of Perilla frutescens leaves (PFL). PFL was fermented for 7 days using six probiotics (Lactobacillus Plantarum SWFU D16, Lactobacillus Plantarum ATCC 8014, Lactobacillus Rhamnosus ATCC 53013, Streptococcus Thermophilus CICC 6038, Lactobacillus Casei ATCC 334, and Lactobacillus Bulgaricus CICC 6045). The total phenol and flavonoid contents, antioxidant abilities, as well as α-glucosidase and acetylcholinesterase inhibition abilities of PFL during the fermentation process were evaluated, and its bioactive compounds were further quantified by high-performance liquid chromatography (HPLC). Finally, non-targeted ultra-HPLC-tandem mass spectroscopy was used to identify the metabolites affected by fermentation and explore the possible mechanisms of the action of fermentation. The results showed that most of the active component contents and functional activities of PFL exhibited that it first increased and then decreased, and different probiotics had clearly distinguishable effects from each other, of which fermentation with ATCC 53013 for 1 day showed the highest enhancement effect. The same trend was also confirmed by the result of the changes in the contents of 12 phenolic acids and flavonoids by HPLC analysis. Further metabolomic analysis revealed significant metabolite changes under the best fermentation condition, which involved primarily the generation of fatty acids and their conjugates, flavonoids. A total of 574 and 387 metabolites were identified in positive ion and negative ion modes, respectively. Results of Spearman's analysis indicated that some primary metabolites and secondary metabolites such as flavonoids, phenols, and fatty acids might play an important role in the functional activity of PFL. Differential metabolites were subjected to the KEGG database and 97 metabolites pathways were obtained, of which biosyntheses of unsaturated fatty acids, flavonoid, and isoflavonoid were the most enriched pathways. The above results revealed the potential reason for the differences in metabolic and functional levels of PFL after fermentation. This study could provide a scientific basis for the further study of PFL, as well as novel insights into the action mechanism of probiotic fermentation on the chemical composition and biological activity of food/drug.
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The objective of the research was to investigate the digestion and fecal fermentation characteristics of the flowers of Juglans regia (FJR), by using in vitro simulated digestion model (oral, gastric, and intestine) as well as colonic fermentation. As a result, the contents of most active substances and functional activities of FJR were decreased as the digestion proceeded, and showed a trend of first increasing and then decreasing in the fecal fermentation phase. In the oral digestion phase, the total phenolic and total flavonoid contents were released most with the values of 11.43 and 9.41 µg/mg, respectively. While in the gastric digestion phase, the antioxidant abilities, α-glucosidase and α-amylase inhibitory abilities were the weakest. By using high-performance liquid chromatography, 13 phenolic acids and 3 flavonoids were detected. Of these, the highest number of identified compounds were found in the undigested and the oral digestion stages, which were mainly salicylic acid, epicatechin, 3,5-dihydroxybenoic acid, vanillic acid, and protocatechuic acid. However, great losses were observed during the gastric and intestinal digestion stages, only epicatechin, salicylic acid, and protocatechuic acid were found. Surprisingly, fecal fermentation released more abundant phenolic substances compared to gastric and intestinal digestion. Additionally, FJR reduced the pH values in the colonic fermentation system, significantly promoted the production of short-chain fatty acids, and regulated the microbe community structure by improving the community richness of beneficial microbiota. This indicated that FJR had the benefit to improve the microorganismal environment in the intestine. Further Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that FJR could suppress the metabolic pathways related to diseases, such as infectious diseases, metabolic diseases and neurodegenerative diseases. In conclusion, although the bioactivities of FJR decreased significantly after in vitro gastrointestinal digestion and fecal fermentation, it still maintained certain antioxidant and hypoglycemic ability in vitro. This study described the detailed changes in the active compounds and bioactivities of FJR during in vitro gastrointestinal digestion and fecal fermentation, and its effects on microbiota composition and SCFAs levels in feces. Our results revealed the potential health benefits of FJR, and could provide a reference for its further research and development.
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Human mesenchymal stem cell (hMSC) homing is the migration of endogenous and exogenous hMSCS to the target organs and the subsequent colonization under the action chemotaxic factors. This is an important process involved in the repair of damaged tissues. However, we know little about the mechanism of hMSC homing. Stromal cell derived factor-1 (SDF-1) is a cytokine secreted by stromal cells. Its only receptor CXCR4 is widely expressed in blood cells, immune cells and cells in the central nervous system. SDF-1/CXCR4 signaling pathway plays an important role in hMSC homing and tissue repair. Human cbll1 gene encodes E3 ubiquitin-protein ligase Hakai (also known as CBLL1) consisting of RING-finger domain that is involved in ubiquitination, endocytosis and degradation of epithelial cadherin (E-cadherin) as well as in the regulation of cell proliferation. We successfully constructed LV3-CXCR4 siRNA lentiviral vector, LV3-CBLL1 RNAi lentiviral vector and the corresponding cell systems which were used to induce hMSC homing in the presence of SKOV3 cells. Thus the mechanism of hMSC homing was studied.