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Background: Changes in gene expression related to obesity are linked to microRNAs, such as miR‐141, which play a crucial role in metabolic homeostasis. Sirtuin 1 (SIRT1), an enzyme that plays a crucial role in regulating various cellular functions and metabolism, is implicated in obesity and the ensuing non‐alcoholic fatty liver disease (NAFLD). The aim of this research was to evaluate the levels of miR‐141 and its relationship with SIRT1 and NAFLD. Methods: A group of 100 adults (50 with obesity and 50 with normal‐weight) were selected and underwent complete clinical evaluation and anthropometric measurements. Biochemical parameters were assessed in blood serum, and the levels of miR‐141 in plasma were measured by real‐time PCR. The expression of the SIRT1 gene was also evaluated in the peripheral blood mononuclear cells using Real‐time PCR. The ELISA technique was used to determine insulin levels. Liver steatosis was assessed by ultrasound. Results: The results showed that levels of miR‐141 were significantly increased in participants with obesity compared with the control group. Conversely, the expression of the SIRT1 gene in individuals with obesity was lower than that in control participants. A strong negative correlation was observed between miR‐141 and SIRT1 and a strong positive association was observed between miR‐141 and metabolic parameters. Furthermore, participants with fatty liver had significantly elevated levels of miR‐141 gene expression and lower expression of SIRT1 gene, compared to those without fatty liver. Conclusion: elevated levels of miR‐141 in individuals with obesity might be a contributing factor in the repression of SIRT1 in obesity and its consequences, including NAFLD. Therefore, miR‐141 might serve as a suitable diagnostic and therapeutic target in obesity and NAFLD. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic inflammation mediated by autoimmune responses. MEG3, a kind of long noncoding RNA (lncRNA), participates in cell proliferation in cancer tissues. However, the correlation between MEG3 and RA is yet unclear. Therefore, to clarify how MEG3 works in RA, we performed a series of experiments using RA samples. We found that MEG3 was downregulated in the fibroblast‐like synoviocytes of RA patients (RA‐FLS), in comparison with healthy subjects. MEG3 was also down‐regulated evidently in lipopolysaccharide (LPS)‐treated chondrocyte. As part of our experiments, MEG3 was overexpressed in chondrocyte by transfection with lentivirus containing sequences encoding MEG3. In addition, in presence of LPS, reductions were identified not only in the cell proliferation, but also in the generation of interleukin‐23 (IL‐23), which, however were reversed in the lentivirus (containing MEG3‐encoding sequences)‐transfected chondrocytes. Up‐regulated MEG3 resulted in an increase the level of Ki67. Moreover, MEG3 was negatively correlated with miR‐141, and miR‐141 was up‐regulated in LPS‐treated chondrocyte. Inhibitory effects of MEG3 overexpression, mentioned above, were partially abolished by overexpressed miR‐141. Further, animal experiment also showed the inhibitory effect of MEG3 in overexpression on the AKT/mTOR signaling pathway. In‐vivoexperiments also showed that cell proliferation was facilitated by MEG3 overexpression with inhibited inflammation. In summary, the protective role of MEG3 in RA was proved to be exerted by the increase in the rate of proliferation, which might correlate to the regulatory role of miR‐141 and AKT/mTOR signal pathway, suggesting that MEG3 holds great promise as a therapeutic strategy for RA. [ABSTRACT FROM AUTHOR]

Background: miR‐141, known as a tumor suppressive microRNA, is downregulated in breast cancer. However, recent contrasting studies report that it also acts as oncogene when it is upregulated. The present study aimed to investigate whether miR‐141 is a tumor suppressor or oncogenic when it reaches normal levels in chitosan/miR‐141 nanoplexes. Methods: Chitosan nanoplexes were prepared using simple complexation method. Nanoplexes were characterized by a gel retardation assay and zeta potential and particle size measurements. To determine the expression level of miR‐141, a quantitative real‐time polymerase chain reaction was performed. The effects of miR‐141 mimics were investigated with respect to angiogenesis by vascular endothelial growth factor (VEGF), epithelial–mesenchymal transition (EMT) by E‐cadherin, metastasis by Igfbp‐4 and Tinagl1 enzyme‐linked immunosorbent assays, invasion by an invasion chamber, and apoptosis by Annexin V. Results: The miR‐141 expression levels of MDA‐MB‐231 and MDA‐MB‐435 cells by administration of chitosan/mimic miR‐141 nanoplexes reached endogenous miR‐141 levels of a non‐tumorigenic epithelial breast cell line, MCF‐10A. According to our results, metastasis, VEGF, EMT and invasion in breast cancer cells were diminished, whereas apoptosis increased by 1.5‐ and 2.4‐fold in breast cancer cell lines as a result of the miR‐141 mimics. Conclusions: In conclusion, we have demonstrated that administration of miR‐141 mimics at the determined doses to breast cancer cells revealed a tumor suppressor effect, and not the oncogenic face. The delivery of miR‐141 by chitosan nanoplexes presents a promising approach for the suppression of breast cancer. [ABSTRACT FROM AUTHOR]

Key points: Endocrine gland‐derived vascular endothelial growth factor (EG‐VEGF) is a critical factor that facilitates trophoblast invasion in placenta.Plasma miR‐141 and miR‐200a levels were elevated, while EG‐VEGF was decreased in peripheral blood and placenta of preeclamptic patients. Furthermore, numbers of cilia in the placenta from preeclamptic women were significantly decreased.Elevated miR‐141 and miR‐200a inhibited the expression of EG‐VEGF, downstream extracellular signal‐regulated kinase (ERK)/matrix metalloproteinase 9 signalling and cilia formation, thus leading to defective trophoblast invasion.The growth of the primary cilium, which transduced ERK signalling upon EG‐VEGF induction for proper trophoblast invasion, was also inhibited by miR‐141 and miR‐200a upregulation. Preeclampsia is a severe gestational complication, and inadequate trophoblast invasion during placental development is an important pathoaetiology. Endocrine gland‐derived vascular endothelial growth factor (EG‐VEGF) is a critical factor that facilitates trophoblast invasion in placenta. By binding to the primary cilium, EG‐VEGF initiates the signalling cascade for proper embryo implantation and placental development. The miR‐200 family was predicted to target the EG‐VEGF 5′‐untranslated region, and its specific binding site was confirmed using a dual luciferase and a co‐transfection assay. In the peripheral blood and placenta of preeclamptic patients, EG‐VEGF showed significantly lower expression, whereas plasma miR‐141 and miR‐200a had higher expression compared with the controls. The biological significance of miR‐141 and miR‐200a was verified using an overexpression method in a trophoblast cell line (HTR‐8/SVneo). Elevated miR‐141 and miR‐200a inhibited the expression of EG‐VEGF, matrix metalloproteinase 9 (MMP9) and downstream extracellular signal‐regulated kinase (ERK) signalling, thus leading to defective trophoblast invasion. Additionally, the growth of the primary cilium, which transduces ERK/MMP9 signalling upon EG‐VEGF induction, was inhibited by miR‐141 and miR‐200a upregulation. Furthermore, the number of cilia in the human placenta of preeclamptic women was significantly decreased compared to normal placenta. In conclusion, the study uncovers the clinical correlations among the miR‐200 family, EG‐VEGF and the primary cilium in preeclampsia and the underlying molecular mechanisms. The results indicate that miR‐141 and miR‐200a directly targeted EG‐VEGF, suppressed primary cilia formation and inhibited trophoblast invasion. Thus, miR‐141 and miR‐200a could be explored as promising miRNA biomarkers and therapeutic targets in preeclampsia. Key points: Endocrine gland‐derived vascular endothelial growth factor (EG‐VEGF) is a critical factor that facilitates trophoblast invasion in placenta.Plasma miR‐141 and miR‐200a levels were elevated, while EG‐VEGF was decreased in peripheral blood and placenta of preeclamptic patients. Furthermore, numbers of cilia in the placenta from preeclamptic women were significantly decreased.Elevated miR‐141 and miR‐200a inhibited the expression of EG‐VEGF, downstream extracellular signal‐regulated kinase (ERK)/matrix metalloproteinase 9 signalling and cilia formation, thus leading to defective trophoblast invasion.The growth of the primary cilium, which transduced ERK signalling upon EG‐VEGF induction for proper trophoblast invasion, was also inhibited by miR‐141 and miR‐200a upregulation. [ABSTRACT FROM AUTHOR]

Micro RNAs (mi RNAs) regulate many cellular activities, including cancer development, progression, and metastasis. Some mi RNAs are involved in breast cancer ( BC) migration and invasion, thus affect patients' prognosis. Microarray analysis was performed to compare mi RNA expression in BC tissues, and results confirmed by qPCR. BC cell migration and invasion were studied in vitro with MDA- MB-231 cells using microplate transwell assays. mi RNA targeting was investigated using luciferase assays, qPCR, and Western blot analysis in cells with overexpression of mi RNA mimics. Knockdown of mi RNA targets was performed using target si RNA lentiviral infection. Results show that micro RNA-141 (miR-141) was downregulated in breast cancer tumor tissues compared with matched surrounding tissues. Downregulation of miR-141 expression correlated with tumor stage, lymph node involvement, and expressions of PCNA, Ki67, and HER2. Overexpression of miR-141 inhibited BC cell proliferation, migration, and invasion in vitro. ANP32E gene was selected as one putative target for further studies based on results from in silico analysis. Results from a dual-luciferase reporter system suggested ANP32E as a direct target of miR-141. Overexpression of miR-141 downregulated ANP32E expression at both mRNA and protein levels in BC cells. Knockdown of ANP32E inhibited BC cell proliferation, migration, and invasion in vitro, mimicking the effect of the overexpression of miR-141. Our study revealed important roles miR-141 plays in BC growth and metastasis. Moreover, for the first time, we identified ANP32E as one of the miR-141 targets, and demonstrated its involvement in the regulation of cell proliferation, migration, and invasion. [ABSTRACT FROM AUTHOR]

Background Recent studies found that gastric cancer patients with Helicobacter pylori infection had a better response to chemotherapy and had an improved overall prognosis compared with those without. However, the underlying mechanism remains unknown. Methods Quantitative real-time PCR ( qRT- PCR) was utilized to determine the expression profile of miR-141 in H. pylori infected cells and tissues and their respective controls. qRT- PCR and Western blot were used to determine the expression level of KEAP-1. Luciferase reporter assays were used to determine whether KEAP-1 was a direct target of miR-141 in the gastric cancer cells. MTT and apoptosis assay were performed to detect the survival of cells under cisplatin treatment. Result We found that H. pylori infection can significantly down-regulate miR-141 expression. Knockdown miR-141 expression in 7901/ DDP and 7901 cells could significantly improve cisplatin sensitivity. Over-expression of miR-141 resulted in enhanced resistance to cisplatin in both gastric cancer cells. We also demonstrated that miR-141 directly targets KEAP1 by luciferase reporter assay, and that down-regulation of KEAP1 induces cisplatin resistance. Conversely, over-expression of KEAP1 significantly enhanced cisplatin sensitivity. Our 75 pairs of tissues also showed that KEAP1 was significantly up-regulated in H. pylori-positive tissues. Conclusion Altogether, these findings demonstrated that the H. pylori infection could modulate cisplatin sensitivity through miR-141-mediated regulation of KEAP1. [ABSTRACT FROM AUTHOR]