Exosomal miRNA-107 induces myeloid-derived suppressor cell expansion in gastric cancer.

  Background: Myeloid-derived suppressor cells (MDSCs) promote immunosuppression in the tumor microenvironment, support tumor growth and survival, and may contribute to immunotherapy resistance. Recent studies showed that tumor-derived exosomes (TDEs) can induce MDSCs accumulation and expansion, the mechanisms of which are largely unknown. Methods: The morphologies and sizes of the exosomes was observed by using a JEM-1400 transmission electron microscope. MicroRNA(miR)-107 and ARG1, DICER1, PTEN, PI3K, AKT, mTOR, and NF-kB mRNAs were quantified by quantitative reverse tanscription PCR. Dual-Luciferase Reports Assay were used to examine the expression of genes which was targeted by miR-107. The expression of proteins were analyzed by using western blot. Results: MiR-107 was not only overexpressed in gastric cancer cells but also enriched in their secreted TDEs. Also, these miR-107 enriched TDEs could be taken up by HLA-DR-CD33+MDSCs, where miR-107 was able to target and suppress expression of DICER1 and PTEN genes. Dampened DICER1 expression supported expansion of MDSCs , while decreased PTEN led to activation of the PI3K pathway, resulting in increased ARG1 expression. Furthemore, gastric cancer-derived miR-107 TDEs, when dosed intravenously into mice, were also capable of inducing expansion of CD11b+Gr1+/high MDSCs in mouse peripheral blood and altering expression of DICER1, PTEN, ARG1, and NOS2 in the MDSCs. Conclusions: Our findings demonstrate for the first time that gastric cancer-secreted exosomes are able to deliver miR-107 to the host MDSCs where they induce their expansion and activition by targeting DICER1 and PTEN genes, thereby may provide novel cancer therapeutics target for gastric cancer.

Changes in serum miRNA-let-7 level in children with attention deficit hyperactivity disorder treated by repetitive transcranial magnetic stimulation or atomoxetine: An exploratory trial.

We aimed to investigate whether microRNA-let-7d (miRNA-let-7d) and miRNA-107 may serve as diagnostic and therapeutic biomarkers of attention deficit hyperactivity disorder (ADHD). The relative expression level of miRNA-let-7d and miRNA-107 in patients with ADHD and in a healthy control group was detected by real-time polymerase chain reaction. The blood samples were collected at 6 weeks after repetitive transcranial magnetic stimulation (rTMS) or atomoxetine (ATX) in ADHD patients, and the relative expression levels of the two miRNAs before and after treatments were compared. There were significant differences in the expression level of miRNA-let-7d between ADHD patients and healthy children, as well as before and after rTMS or ATX treatment in ADHD patients. However, the expression of miRNA-107 showed no significant difference between ADHD patients and healthy children or before and after rTMS (or ATX treatment). These results suggest that serum miRNA-let-7d may serve as a potential diagnostic and therapeutic biomarker for children with ADHD.

Mesenchymal stem cells alleviate acute kidney injury via miR-107-mediated regulation of ribosomal protein S19.

BACKGROUND: The characteristics of mesenchymal stem cells (MSCs) in the repair of acute kidney injury (AKI) have been extensively studied. However, some potential molecular mechanisms remain indistinct. The aim of this study was to combine published microRNA (miRNA) transcriptional profiling with quantitative proteomic analyses to reveal specific miRNAs or genes for MSC-based therapy in AKI. METHODS: Transcriptome data containing significantly changed miRNAs in renal tissue from AKI mice treated with and without MSCs were downloaded. Proteomics resources were downloaded from a human proximal renal tubule cell line (HK-2) that served as a good in vitro model for AKI treated with MSCs. We connected the proteomics data with transcriptional records based on miRNA function. Differentially expressed genes (DEGs) were sorted. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted, and protein-protein interaction (PPI) chains were formed. The genes identified in the analyses were verified in a cisplatin-induced AKI rat model and in HK-2 cells exposed to cisplatin and cocultured with MSCs. RESULTS: A total of 207 specific DEGs were sorted. The ribosomal pathway was identified in pathway enrichment, and ribosomal proteins were identified from the PPI network complex. The targeting of the microRNAs, miR-107 to RPS19, was directly verified by the dual-luciferase method. miR-107 knockdown induced RPS19 expression, protected HK-2 cells from cisplatin-induced apoptosis, and promoted cell proliferation. CONCLUSIONS: By analyzing comprehensive bioinformatics data, we have confirmed the DEGs and pathways in AKI treated with MSCs. Bone marrow-derived MSCs reduce miR-107 expression and increase RPS19 expression by repressing the proliferation of cisplatin-induced AKI cells and initiating apoptosis.

Are miRNA-103, miRNA-107 and miRNA-122 Involved in the Prevention of Liver Steatosis Induced by Resveratrol?

The aim of the present study was to determine whether the reduction in liver fat previously observed in our laboratory in a cohort of rats which had been fed an obesogenic diet was mediated by changes in the expression of microRNA (miRNA)-103-3p, miRNA-107-3p and miRNA-122-5p, which represent 70% of total miRNAs in the liver, as well as in their target genes. The expression of the three analysed miRNAs was reduced in rats treated with resveratrol. A reduction in sterol-regulatory element binding protein 1 (SREBP1) and an increase in carnitine palmitoyltransferase 1a (CPT1a) were observed in resveratrol-treated rats. No changes were found in fatty acid synthase (FAS). In cultured hepatocytes, SREBP1 protein was increased after the transfection of each miRNA. FAS protein expression was decreased after the transfection of miRNA-122-5p, and CPT1a protein was down-regulated by the over-expression of miRNA-107-3p. This study provides new evidences which show that srebf1 is a target gene for miRNA-103-3p and miRNA-107-3p, fasn a target gene for miRNA-122-5p and cpt1a a target gene for miRNA-107-3p. Moreover, the reduction in liver steatosis induced by resveratrol in rats fed an obesegenic diet is mediated, at least in part, by the increase in CPT1a protein expression and activity, via a decrease in miRNA-107-3p expression.

Expression of miRNA-21, miRNA-107, miRNA-137 and miRNA-29b in meningioma.

OBJECTIVE: Meningiomas are among the most common intracranial tumors, accounting for 30% of all tumors of the central nervous system. Recent studies analyzing microRNA (miRNA) profiles and functions in cancer have provided valuable information about the molecular pathogenesis of several tumor types, including glioblastoma multiforme (GBM), hepatocellular carcinoma, and breast, lung, colon, and prostate cancer. miRNAs are a family of small, endogenous, noncoding RNAs of 18-25 nucleotides. In this study, we carried out a genome-wide array screen comparing miRNA-21, miRNA-107, miRNA-137 and miRNA-29b expression in meningiomas. PATIENTS AND METHODS: A total of 50 meningioma patients (16 men and 34 women) aged between 32 and 80 years were included. The study was conducted at Istanbul Research and Training Hospital Neurosurgery Clinic. RESULTS: Our results have shown a significant increase in miRNA-21 expression with increasing histopathologic grade, while there was a significant reduction in miRNA-107 expression with the increasing histopathological grade. miRNA-137 and miRNA-29b expression did not differ significantly according to histopathologic grade. CONCLUSION: The subject of our study, i.e. the association between miRNA expression and meningioma, is continuously gaining more importance in the wider context of the recent developments in genetic treatments.

Osthole reduced Aβ synthesis by up-regulatingmiRNA-107 in neurons transfected with APP595/596 gene / 中国药理学通报

Aim To investigate the neuroprotective effects of osthole(Ost)on the primary cultured cortical neurons transfected with APP595/596 gene and its underlying mechanism.Methods Neonatal mouse cortical neurons were transfected with APP595/596 gene to establish AD cell models for the further study.Then,the cell viability was detected by CCK-8 assay,and the leakage of lactate dehydrogenase(LDH)was assayed by LDH kit to evaluate the injury degree.Transferase-mediated nick end labeling(TUNEL)was used to evaluate the cell apoptosis.The expression of β-amyloid peptide(Aβ)and β-site APP cleaving enzyme 1(BACE1)was measured by immunofluorescence,while the miRNA-107 was measured by RT-PCR.Results Compared to model group,Ost could significantly improve the neurons viability,decrease the LDH release and prevent the apoptosis.Ost also inhibited the expression of Aβ and BACE1 at protein level,while enhanced the expression of miRNA-107 at gene level.Conclusion Ost plays a neuroprotective role in neurons transfected with APP595/596 gene in part through up-regulating miRNA-107.

Osthole decreases beta amyloid levels through up-regulation of miR-107 in Alzheimer's disease.

Accumulation of ß-amyloid peptide (Aß) in the brain plays an important role in the pathogenesis of Alzheimer's disease (AD). Although osthole has been shown to neuroprotective activity in AD, the exact molecular mechanism of its neuroprotective effects has not yet been fully elucidated. Recently, microRNAs (miRNAs) have been reported to regulate multiple aspects of AD development and progression, indicating that targeting miRNAs could be a novel strategy to treat AD. In the current study, we investigated whether a natural coumarin derivative osthole could up-regulate miR-107, resulting in facilitating the cells survival, reducing LDH leakage, inhibiting apoptosis and reducing beta amyloid (Aß) production in AD. We found that osthole treatment significantly up-regulate miR-107 expression and inhibited BACE1, one of the targets of miR-107. Administration of osthole to APP/PS1 transgenic mice resulted in a significant improvement in learning and memory function, which was associated with a significant a decrease in Aß in the hippocampal and cortex region of the brain. Our findings demonstrated that osthole plays a neuroprotective activity role in part through up-regulate miR-107 in AD.