A microRNA signature for early detection and RNA therapy in Alzheimer´s disease (miR-148a-3p)
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PROVIDER: PRJNA641433 | ENA |
REPOSITORIES: ENA
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Project description:Post-transcriptional regulation of genes is heavily dependent on the action of miRNAs. miRNAs take part in various cellular processes and have been shown to be crucial in oncogenesis. Identification of miRNA targets is crucial for understanding its functions in different cellular contexts. miR-148a-3p is highly expressed in HCT116 cells and several other cell lines. However, the studies about mRNA targetting activitiy of this miRNA was limited. In this study, we aimed at identifying target repotoire of miR-148a-3p by using HCT116 DROSHA-KO model. We found several genes that are under miR-148a-3p regulation, including several reported targets. We next found the negative association between miR-148a-3p and DDX6, one of the identified gene, in leukemia. We examined DDX6 functions in this cancer and showed that the depletion of DDX6 helps impair leukemia cell growth, promote apoptosis and increase survival rate of transplanted mice. We then identified that DDX6 functions to suppress TXNIP, a well known tumor suppressor in leukemia and various types of cancer. Our findings uncovered the regulation axis between miR-148a-3p/DDX6/TXNIP in leukemia which provides molecular mechanism basis for therapeutic treatment directions.
2022-06-07 | GSE201905 | GEO
Project description:Since changes in cognitive function develop slowly over time, Alzheimer’s disease patients are often diagnosed at an advanced stage of molecular pathology, a time point when causative treatments fail. Thus, there is great need for inexpensive and minimal invasive biomarker that could be used in screening approaches with the aim to identify individuals at risk, that can then undergo further diagnostics and eventually stratified therapies. In this study we use an integrative approach combining the analysis of human data and model systems to identify a circulating 3-microRNA signature that reflect key processes linked to neural homeostasis and informs about cognitive decline. We furthermore provide evidence that expression changes of this signature represent relevant patho-mechanisms in the brain and are a suitable target for RNA therapeutics towards dementia.
2021-08-17 | GSE153106 | GEO
Project description:Purpose: To investigate the regulatory role of microRNA (miR)-148a-3p in mouse corpus cavernous pericyte (MCPs)-derived extracellular vesicles (EVs) in the treatment of diabetes-induced erectile dysfunction (ED). Materials and Methods: Mouse corpus cavernous tissue was used for MCPs primary culture and EVs isolation. Small RNA sequencing analysis was performed to assess the type and content of miRs in MCPs-EVs. Four groups of mice were used: control nondiabetic mice and streptozotocin-induced diabetic mice receiving two intracavernous injections (days -3 and 0) of phosphate buffered saline, MCPs-EVs transfected with regent control, or MCPs-EVs transfected with miR-148a-3p inhibitor. The function of miR-148a-3p in MCPs-EVs was evaluated by tube formation assay, migration assay, TUNEL assay, intracavernous pressure, immunofluorescence staining, and western blot experiments. Results: We extracted EVs from MCPs and by small RNA sequencing analysis we found that miR-148a-3p is enriched in MCPs-EVs. Exogenous administration of MCPs-EVs can effectively promote mouse cavernous endothelial cell (MCECs) tube formation, migration, proliferation, and reduce MCECs apoptosis under high-glucose conditions. However, these effects are significantly attenuated in miR-148a-3p-depleted MCPs-EVs, which is extracted after inhibiting miR-148a-3p expression in MCPs. Repeated intracavernous injections of MCPs-EVs improves erectile function by inducing cavernous neurovascular regeneration in diabetic mice. Through online bioinformatics databases and luciferase report assays, we predict Pyruvate dehydrogenase kinase-4 (PDK4) is a potential target gene of miR-148a-3p. Conclusions: Our findings provide new and reliable evidence that miR-148a-3p in MCPs-EVs significantly enhances cavernous neurovascular regeneration by inhibiting PDK4 in diabetic mice.
2023-12-19 | GSE195533 | GEO
Project description:A quantitative proteomics combined with stable isotope labeling was applied to identify the global profile of miR-148a-regulated downstream proteins in AGS cancer cells. For proteomic analysis, cells were treated with miR-148a mimic (Pre-miR-148a) or miR-148a negative control (miR-CTL) and the downstream protein expression level (Pre-miR-148a/miR-CTL) were quantified using iTRAQ approach. Bioinformatics pipeline: The peak list in the resultant MS/MS spectra were generated by Mascot Distiller v2.1.1.0 and searched using Mascot v2.2 against the International Protein Index (IPI) human database (v. 3.64, 84032 sequences). The Mascot search parameters were +-0.1 Da for MS tolerance, +-0.1 Da for MS/MS mass tolerance, allowances for two missed cleavages, and variable modifications of deamidation (NQ), oxidation (M), iTRAQ (N terminal), iTRAQ (K), and MMTS (C). Protein quantitation were calculated using the Multi-Q software v1.6.5.4 with a dynamic range filter of ion count > 30.
2013-07-24 | PXD000190 | Pride
Project description:miR-148a-3p and DDX6 functional link promotes survival of myeloid leukemia cells
| PRJNA833443 | ENA
Project description:Expression profiling of miR-32 or miR-148a transfected LNCaP cells.
2012-03-29 | E-MEXP-2943 | biostudies-arrayexpress
Project description:This is a prospective-retrospective study to determine if the expression of the miRNA’s miR-31-3p and miR-31-5p are prognostic of patient outcomes or predictive of the benefit from anti-EGFR therapy in stage III Colon Cancer. The present study will utilize FFPE tumor samples collected from patients enrolled in the PETACC-8 study conducted by the Fédération Francophone de Cancérologie Digestive (FFCD). This phase 3 clinical trial prospectively randomized fully resected stage III colon cancer patients to receive adjuvant treatment with either FOLFOX-4 plus cetuximab or FLOFOX-4 alone.
| 2260465 | ecrin-mdr-crc
Project description:In the current study, we characterized the global miRNA expression profile in mouse pancreatic acinar cells during acute pancreatitis using next-generation RNA-Sequencing. We identified 330 known and 6 novel miRNAs being expressed in mouse pancreatic acinar cells. At basal state, miR-148a-3p, miR-375-3p, miR-217-5p, miR-216a-5p were among the most abundantly expressed whereas miR-24-5p and miR-421-3p were least abundant. Treatment of acinar cells with supra-maximal caerulein or bile acid induced numerous changes in miRNA expression levels. In particular, we observed significant upregulation of miR-21-3p in these experiments, which was further, confirmed using mouse models of acute pancreatitis. In summary, this is the first comprehensive analysis of miRNA expression in healthy mouse pancreatic acinar cells and how this expression signature changes in acute pancreatitis.
2016-10-25 | GSE81260 | GEO
Project description:Comparision of HeLa cells transfected with miR-148a mimic or scramble control for 48h
2015-01-13 | E-MTAB-2411 | biostudies-arrayexpress
Project description:Long-lived antibody-secreting plasma cells are essential to establish humoral memory against pathogens. While a plasma cell gene signature has been established, elaborate key regulators remain enigmatic.The plasma cell signature microRNA miR-148a favors in vitro differentiation of plasmablasts by repressing the germinal center transcription factor Bach2 and pro-apoptotic BIM and PTEN. To determine whether miR-148a fine-tunescontrols the in vivo development of B cells into long-lived plasma cells, we established mice with a genomic, conditional and inducible deletion of miR-148a. The analysis of miR-148a-deficient mice revealed reduced serum Ig, decreased numbers of newly formed plasmablasts and a reduced CD19-negative, CD93-positive long-lived plasma cells compartment. RNASeq and metabolic analysis showed an impaired glucose uptake and oxidative phosphorylation-based energy metabolism, altered abundance of homing receptors CXCR3 (increase) and CXCR4 (reduction) in miR-148a-deficient plasma cells. These findings establish the importance of miR-148a as a regulator of the differentiation and maintenance of late CD19-negative mature plasma cells by controlling their metabolism and retention in the bone marrow niche. clearly undermine our model of miR-148a as a regulator of the maintenance of long-lived plasma cells.
2021-05-21 | GSE156002 | GEO