• Diagnosis
• Exosome
• Glioblastoma
• Glioma
• MiRNA
• Prognosis

• Humans
• Exosomes/metabolism
• Glioblastoma/diagnosis
• Glioblastoma/therapy
• Glioblastoma/metabolism
• Brain Neoplasms/diagnosis
• Brain Neoplasms/therapy
• Brain Neoplasms/metabolism
• Tumor Microenvironment/physiology
• Biomarkers, Tumor/metabolism
• Animals
• Blood-Brain Barrier/metabolism

• antimetastatic
• micell/liposome
• microRNAs
• silibinin
• wound healing

• Islamic Azad University

• Aging
• Brain
• Estrogen
• Ovariectomy
• miRNA

• Biomarker
• cancer
• miR-181a
• microRNA
• microRNA processing
• microRNA regulation
• microRNA therapeutics
• signaling pathways

• Humans
• Neoplasms/genetics
• Neoplasms/pathology
• Neoplasms/therapy
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Signal Transduction
• Tumor Microenvironment
• Animals
• Biomarkers, Tumor/metabolism
• Biomarkers, Tumor/genetics
• Molecular Targeted Therapy
• Gene Expression Regulation, Neoplastic
• Precision Medicine
• Cell Proliferation
• Apoptosis

• R01 CA197780 NCI NIH HHS

• Brain Cancer
• Epigenetics/ Epigenomics
• Genomics
• Glioblastoma
• Glioma
• Signaling pathway

• Glioblastoma/genetics
• Glioblastoma/metabolism
• Humans
• Brain Neoplasms/genetics
• Brain Neoplasms/metabolism
• Transcriptome
• Epigenesis, Genetic/genetics
• Epigenomics
• Genomics
• Signal Transduction/genetics
• Gene Expression Regulation, Neoplastic/genetics
• Mutation

• PAX8‐AS1
• TC
• TIMP3
• ceRNA
• hsa‐miR‐181b‐5p
• tumor immunity

• Natural Science Foundation of Hubei Province
• Applied Fundamental Research of Wuhan
• National Natural Science Foundation of China

• Apoptosis
• Asprosin
• Cell viability
• Diabetes
• Dorsal root ganglion
• miRNA-181a

• Humans
• Ganglia, Spinal
• Neurons
• Diabetes Mellitus/metabolism
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Glucose/metabolism

• 119S138. Türkiye Bilimsel ve Teknolojik Araştırma Kurumu

• Glioblastoma multiforme
• Layer-by-layer
• Lipid nanoparticles
• microRNA-181a-5p

• Humans
• Glioblastoma/genetics
• Glioblastoma/therapy
• Glioblastoma/metabolism
• Hyaluronic Acid
• Cell Line, Tumor
• MicroRNAs/genetics
• MicroRNAs/metabolism
• Lipids
• Cell Proliferation

• CIHR 475599 CIHR

• Neuroinflammation
• glioblastoma
• glioma
• inflammation
• miRNA
• microRNA
• non-coding RNA
• oncogene
• oncomir
• schizophrenia
• tumor suppressor

• Humans
• Methylation
• Ribose
• Intellectual Disability/genetics
• Methyltransferases/genetics
• RNA, Transfer/genetics
• RNA, Transfer/metabolism
• Neurons/metabolism
• Nuclear Proteins/genetics

• Agence Nationale de la Recherche (ANR)
• Fondation Maladies Rares (FMR)
• Sorbonne Université (Sorbonne University)
• Deutsche Forschungsgemeinschaft (DFG)
• Fondation pour la Recherche Médicale (FRM)
• Ligue National contre le cancer Île de France

• Brain health
• Gallic acid; neuroprotective activity; pharmacological effects
• Molecular mechanisms

• Glioma
• IFI30
• Propofol
• circ_0047688
• miR-516b-5p

Gliomas are the most invasive brain tumors characterized by high mortality and recurrence rates. Glioblastoma (GBM), a grade IV brain tumor, is known for its heterogeneity and resistance to therapy. Modern diagnostics of various forms of malignant brain tumors is carried out mainly by imaging methods, such as magnetic resonance imaging, electroencephalography, positron emission tomography, and tumor biopsy is also used. The disadvantages of these methods are their inaccuracy and invasiveness, which entails certain risks for the patient's health, so modern science has stepped up the search for more reliable and safe methods for diagnosing gliomas, including the search for novel biomarkers. MicroRNA (miRNAs), a class of small non-coding RNA, perform the most important functions in various biological processes. In recent years, great progress in the study of miRNAs paths associated with the GBM pathogenesis has been achieved. MiRNAs molecules were identified as diagnostic and prognostic biomarkers, and can also serve as therapeutic targets and agents. This review provides current knowledge about the role of miRNAs in the pathogenesis of glial brain tumors, as well as the potential use of miRNAs as diagnostic and therapeutic targets for gliomas.

Gliomas are central nervous system tumors with a lethal prognosis. Small micro-RNA molecules participate in various biological processes, are tissue-specific, and, therefore, could be promising targets for cancer treatment. Thus, this study aims to examine miR-181a as a potent biomarker for the diagnosis and prognosis of glioma patients and, for the first time, to find associations between the expression level of miR-181a and patient quality of life (QoL) and cognitive functioning. The expression level of miR-181a was analyzed in 78 post-operative II-IV grade gliomas by quantitative real-time polymerase chain reaction. The expression profile was compared with patient clinical data (age, survival time after the operation, tumor grade and location, mutation status of isocitrate dehydrogenase 1 (IDH1), and promoter methylation of O-6-methylguanine methyltransferase). Furthermore, the health-related QoL was assessed using the Karnofsky performance scale and the quality of life questionnaires; while cognitive assessment was assessed by the Hopkins verbal learning test-revised, trail-making test, and phonemic fluency tasks. The expression of miR-181a was significantly lower in tumors of grade III and IV and was associated with IDH1 wild-type gliomas and a worse prognosis of patient overall survival. Additionally, a positive correlation was observed between miR-181a levels and functional status and QoL of glioma patients. Therefore, miR-181a is a unique molecule that plays an important role in gliomagenesis, and is also associated with changes in patients’ quality of life.

• Biomarkers
• Exosome
• Glioblastoma multiforme
• Immunotherapy
• MicroRNA

• Tabriz University of Medical Sciences

• Glioblastoma multiforme
• MiRNA
• prediction
• prognosis
• response

• Brain Neoplasms/diagnosis
• Brain Neoplasms/genetics
• Brain Neoplasms/pathology
• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic
• Glioblastoma/diagnosis
• Glioblastoma/genetics
• Humans
• MicroRNAs/genetics
• Prognosis

• Affiliated Hospital of Southwest Medical University

miR-181a/b and miR-410 downregulation and miR-155 upregulation has been shown to play important roles in the oncogenesis and progression of gliomas including high-grade gliomas. However, the potential role of plasma miR-181a/b, miR-410 and miR-155 in the diagnosis and prognosis of high-grade gliomas remains poorly known.

We retrieved published articles from the PubMed, the Cochrane Central Register of Controlled Trials, and Web of Science database and obtained different sets of data on microRNAs (miRNAs) expression profiling in glioma and highlighted the most frequently dysregulated miRNAs and their gene-targets (PDCD4, WNT5A, MET, and EGFR) in high-grade gliomas. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was carried out to measure the pre- and postoperative plasma levels of miR-181a/b, miR-410 and miR-155 in 114 Grade 3-4 glioma patients, 77 Grade 1-2 glioma patients and 85 healthy volunteers as control group. The diagnostic and prognostic value of circulating miR-181a/b, miR-410 and miR-155 as biomarker was estimated by the Receiver Operating Characteristic (ROC) curve and the area under the curve (AUC) and Kaplan–Meier analysis.

We found a plasma miRNA signature including three downexpressed miRNAs and one overexpressed (miR-181a, miR-181b and miR-410; miR-155) in high-grade glioma patients in comparison with low-grade glioma patients control group. The ROC curve AUC of these four circulating miRNAs were ≥ 0.75 for high-grade glioma patients in before and after surgery. Higher circulating miR-155 and lower miR-181a/b and miR-410 expression is associated with clinical data, clinic pathological variables, worse overall survival (OS) of patients and negative correlated with potential gene-targets expression. Moreover, Kaplan–Meier analysis showed that miR-181a/b, miR-410 and miR-155 were independent predictors of OS in high-grade glioma patients.

Our data, for the first time, demonstrated that circulating miR-181a/b, miR-410 and miR-155 could be a useful diagnostic and prognostic non-invasive biomarkers in high-grade gliomas.

• cell development
• microRNA
• multiple sclerosis
• myelination
• oligodendrocyte

MicroRNAs (miRNAs) have been revealed to play a crucial role in oncogenesis of esophageal squamous cell carcinoma (ESCC). However, the biological role of miR-181a-5p in ESCC is currently less explored. The current study was designed to assess whether miR-181a-5p affects ESCC progression and further investigate relevant underlying mechanisms. Based on the data of GSE161533, GSE17351, GSE75241 and GSE67269 downloaded from GEO database, MAP2K1 (MEK1) was revealed to be one overlapping gene of the top 300 DGEs. Additionally, using the predicting software, miR-181a-5p was projected as the presumed target miRNA. Immunohistochemical staining and RT-qPCR research revealed that miR-181a-5p expression was decreased in human tumor tissues relative to surrounding peri-cancerous tissues. In an in vivo experiment, miR-181a-5p mimics could inhibit tumor growth and metastasis of ESCC. Gene expression profiles in combination with gene ontology (GO) and KEGG pathway analysis revealed that MAP2K1 (MEK1) gene and ERK-MMP pathway were implicated in ESCC progression. MiR-181a-5p mimics inhibited the activity of p-ERK1/2, MMP2 and MMP9 in vivo, as shown by Western blotting and immunohistochemistry labeling. There were no variations in the expression of p-P38 and p-JNK proteins. Additionally, miR-181a-5p mimics lowered p-ERK1/2, MMP2 and MMP9 levels in ECA109 cells, which were restored by MEK1-OE lentivirus. MEK1-OE Lentivirus significantly reversed the function induced by miR-181a-5p mimics in ECA109 cells. Moreover, further investigation indicated that the capability of migration, invasion and proliferation was repressed by miR-181a-5p mimics in ECA109 cells. In short, repressed ERK-MMP pathway mediated by miR-181a-5p can inhibit cell migration, invasion and proliferation by targeting MAP2K1 (MEK1) in ESCC.

• ESCC
• MEK1
• miR-181a-5p

• MEG3
• TNF
• anal abscess
• inflammation
• miR-181b

Glioblastoma (GBM) as the most common and aggressive brain tumor is characterized by genetic heterogeneity, invasiveness, radio-/chemoresistance, and occurrence of GBM stem-like cells. The metalloprotease-disintegrin ADAM8 is highly expressed in GBM tumor and immune cells and correlates with poor survival. In GBM, ADAM8 affects intracellular kinase signaling and increases expression levels of osteopontin/SPP1 and matrix metalloproteinase 9 (MMP9) by an unknown mechanism. Here we explored whether microRNA (miRNA) expression levels could be regulators of MMP9 expression in GBM cells expressing ADAM8. Initially, we identified several miRNAs as dysregulated in ADAM8-deficient U87 GBM cells. Among these, the tumor suppressor miR-181a-5p was significantly upregulated in ADAM8 knockout clones. By inhibiting kinase signaling, we found that ADAM8 downregulates expression of miR-181a-5p via activation of signal transducer and activator of transcription 3 (STAT3) and mitogen-activated protein kinase (MAPK) signaling suggesting an ADAM8-dependent silencing of miR-181a-5p. In turn, mimic miR-181a-5p transfection caused decreased cell proliferation and lower MMP9 expression in GBM cells. Furthermore, miR-181a-5p was detected in GBM cell-derived extracellular vesicles (EVs) as well as patient serum-derived EVs. We identified miR-181a-5p downregulating MMP9 expression via targeting the MAPK pathway. Analysis of patient tissue samples (n=22) revealed that in GBM, miR-181a-5p is strongly downregulated compared to ADAM8 and MMP9 mRNA expression, even in localized tumor areas. Taken together, we provide evidence for a functional axis involving ADAM8/miR-181a-5p/MAPK/MMP9 in GBM tumor cells.

• ADAM8
• MMP9
• MR spectroscopy
• extracellular vesicles
• glioblastoma
• miR-181a-5p
• miRNA
• tumor microenvironment

• amyotrophic lateral sclerosis (ALS)
• astrocyte-mediated neurotoxicity
• fibroblast-transdifferentiated astrocytes
• inflammatory-associated miRNAs
• miR-146a modulation
• mutant SOD1 (mSOD1)
• patient phenotype subtypes
• small extracellular vesicles (sEVs)
• sporadic ALS (sALS)

• Amyotrophic Lateral Sclerosis/genetics
• Animals
• Astrocytes
• Disease Models, Animal
• Fibroblasts
• Humans
• Mice
• MicroRNAs/genetics
• Neurotoxicity Syndromes

• TURNER/OCT15/972-797 Motor Neurone Disease Association
• JS-BRC-1215-20017 Department of Health

• Chondrocyte
• Osteoarthritis (OA)
• Osteopontin (OPN)
• Proliferation
• lncRNA MIAT
• miR-181a-5p

• brain tumour
• medulloblastoma
• miRNA
• stem cells
• subgroups

• Glioblastoma
• Stem-like state
• Tumorigenesis
• hypoxia microenvironment
• miRNAs

• Brain Neoplasms/genetics
• Brain Neoplasms/metabolism
• Brain Neoplasms/pathology
• Cell Line, Tumor
• Down-Regulation
• Genotype
• Glioblastoma/genetics
• Glioblastoma/metabolism
• Glioblastoma/pathology
• Glucose Transporter Type 1/metabolism
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
• MicroRNAs/metabolism
• Octamer Transcription Factor-3/metabolism
• Phenotype
• Proto-Oncogene Proteins c-bcl-2/metabolism
• SOXB1 Transcription Factors/metabolism
• Survivin/metabolism
• Tumor Hypoxia/genetics
• Tumor Microenvironment/genetics
• Up-Regulation
• Vascular Endothelial Growth Factor A/metabolism

• Collaborative filtering algorithm
• Infer miRNA-disease associations
• Recommender systems
• Resource allocation algorithm
• miRNA-disease-lncRNA tripartite graph

• Algorithms
• Computational Biology/methods
• Genetic Predisposition to Disease
• Glaucoma, Open-Angle
• Humans
• Male
• MicroRNAs/genetics

• Vietnam Ministry of Education and Training

Acute lymphoblastic leukemia (ALL), a malignant transformation and proliferation of the lymphoid line of blood cells, is characterized by chromosomal abnormalities and genetic changes. The purpose of this research was the evaluation of expression level of miR-181a and -b in patients with ALL compared to the control group. Furthermore, we examined their expression level in hematopoietic stem-cell transplantation (HSCT) patients who developed acute graft-versus-host disease (aGVHD) in comparison with those without aGVHD and explore the relationship between their expression level and cytogenetic abnormalities. In this cross-sectional study, 76 newly diagnosed adult De novo ALL patients were enrolled who were admitted to our referral hospital. All patients received standard chemotherapy, consisting of daunorubicin. A total of 37 patients underwent HSCT from the related human leukocyte antigen-matched donors. ALL patients have been diagnosed with the coronavirus disease 2019 (COVID-19) and Torque teno viruses (TTVs). We assessed the expression levels of miR-181a and -b in the peripheral blood sample of ALL patients at the time of diagnosis prior to chemotherapy, and healthy matched individuals by RT–PCR. TTVs and COVID-19 load were also determined via RT–PCR. In conclusion, the expression level of miR-181a and -b were significantly higher in ALL patients than healthy controls and also increased in patients who developed aGVHD in comparison with those without aGVHD. MiR-181a and -b can be a useful biomarker in ALL and a useful indicator of aGVHD. The expression level of miR-181a in ALL patients with COVID-19 is significantly up-regulated, while it is reduced in these patients with TTV.

• Acute lymphoblastic leukemia
• COVID-19
• MicroRNAs
• Torque teno viruses
• aGVHD

• Shiraz University of Medical Sciences

• biotechnology
• noncoding RNAs
• pituitary neoplasms
• tumor biomarker

• Extracellular vesicles
• HCC
• Long non-coding
• Real-time PCR
• miRNA

• Drug resistance
• Exosomes
• Glioblastoma
• Noncoding RNAs

• Bioinformatics analysis
• Cholangiocarcinoma
• Diagnosis and prognosis
• Molecular mechanism
• miR-181b-5p

• EMT
• Glioma
• MGST1
• Snail
• miR-379–5p

• Arginase 1
• Immunosuppression
• MDSCs
• MicroRNA
• Sepsis
• T-lymphocytes

(1) Background: Glioblastoma multiforme (GBM) is among the most aggressive cancers with a poor prognosis. Treatment options are limited, clinicians lack efficient prognostic and predictive markers. Circulating miRNAs—besides being important regulators of cancer development—may have potential as diagnostic biomarkers of GBM. (2) Methods: In this study, profiling of 798 human miRNAs was performed on blood plasma samples from 6 healthy individuals and 6 patients with GBM, using a NanoString nCounter Analysis System. To validate our results, five miRNAs (hsa-miR-433-3p, hsa-miR-362-3p, hsa-miR-195-5p, hsa-miR-133a-3p, and hsa-miR-29a-3p) were randomly chosen for RT-qPCR detection. (3) Results: In all, 53 miRNAs were significantly differentially expressed in plasma samples of GBM patients when data were filtered for FC 1 and FDR 0.1. Target genes of the top 39 differentially expressed miRNAs were identified, and we carried out functional annotation and pathway enrichment analysis of target genes via GO and KEGG-based tools. General and cortex-specific protein–protein interaction networks were constructed from the target genes of top miRNAs to assess their functional connections. (4) Conclusions: We demonstrated that plasma microRNA profiles are promising diagnostic and prognostic molecular biomarkers that may find an actual application in the clinical practice of GBM, although more studies are needed to validate our results.

• NanoString
• biomarker
• blood plasma
• circulating miRNA
• glioblastoma
• network analysis

• Biomarkers, Tumor/genetics
• Biomarkers, Tumor/metabolism
• Case-Control Studies
• Circulating MicroRNA/genetics
• Circulating MicroRNA/metabolism
• Computational Biology
• Gene Expression Profiling
• Gene Regulatory Networks
• Glioblastoma/blood
• Glioblastoma/genetics
• Glioblastoma/pathology
• Humans
• Prognosis
• Protein Interaction Maps

Our previous studies have indicated that miR-198 reduces cellular methylguanine DNA methyltransferase (MGMT) levels to enhance temozolomide sensitivity. Transforming growth factor beta 1 (TGF-β1) switches off miR-198 expression by repressing K-homology splicing regulatory protein (KSRP) expression in epidermal keratinocytes. However, the underlying role of TGF-β1 in temozolomide resistance has remained unknown.

The distribution of KSRP was detected by western blotting and immunofluorescence. Microarray analysis was used to compare the levels of long noncoding RNAs (lncRNAs) between TGF-β1–treated and untreated cells. RNA immunoprecipitation was performed to verify the relationship between RNAs and KSRP. Flow cytometry and orthotopic and subcutaneous xenograft tumor models were used to determine the function of TGF-β1 in temozolomide resistance.

Overexpression of TGF-β1 contributed to temozolomide resistance in MGMT promoter hypomethylated glioblastoma cells in vitro and in vivo. TGF-β1 treatment reduced cellular MGMT levels through suppressing the expression of miR-198. However, TGF-β1 upregulation did not affect KSRP expression in glioma cells. We identified and characterized 2 lncRNAs (H19 and HOXD-AS2) that were upregulated by TGF-β1 through Smad signaling. H19 and HOXD-AS2 exhibited competitive binding to KSRP and prevented KSRP from binding to primary miR-198, thus decreasing miR-198 expression. HOXD-AS2 or H19 upregulation strongly promoted temozolomide resistance and MGMT expression. Moreover, KSRP depletion abrogated the effects of TGF-β1 and lncRNAs on miR-198 and MGMT. Finally, we found that patients with low levels of TGF-β1 or lncRNA expression benefited from temozolomide therapy.

Our results reveal an underlying mechanism by which TGF-β1 confers temozolomide resistance. Furthermore, our findings suggest that a novel combination of temozolomide with a TGF-β inhibitor may serve as an effective therapy for glioblastomas.

• KSRP
• MGMT
• TGF-β1
• glioblastoma
• temozolomide resistance

• ANP32A
• Chicken
• Marek’s disease
• gga-miR-181a

Hypoxia is a common feature of solid tumors, and develops because of the rapid growth of the tumor that outstrips the oxygen supply, and impaired blood flow due to the formation of abnormal blood vessels supplying the tumor. It has been reported that tumor hypoxia can: activate angiogenesis, thereby enhancing invasiveness and risk of metastasis; increase survival of tumor, as well as suppress anti-tumor immunity and hamper the therapeutic response. Hypoxia mediates these effects by several potential mechanisms: altering gene expression, the activation of oncogenes, inactivation of suppressor genes, reducing genomic stability and clonal selection. We have reviewed the effects of hypoxia on tumor biology and the possible strategiesto manage the hypoxic tumor microenvironment (TME), highlighting the potential use of cancer stem cells in tumor treatment.

• Cancer progression
• Cancer stem cells
• Hypoxia
• Tumor microenvironment
• Tumor treatment

MicroRNAs can silence a broad set of target genes that may benefit heterogeneous tumors like glioblastoma. We have previously shown that osteopontin has an oncogenic role and may have immune modulatory effects on macrophages. In the current study, we used miRNAs to target osteopontin in tumor cells and modulate immune cells to elicit an antitumor effect. Intravenous delivery of miR-181a to immune competent mice bearing intracranial glioblastoma demonstrated a 22% increase in median survival duration relative to that of control mice. The overexpression of miR-181a in tumor cells led to decreased OPN production and proliferation and increased apoptosis in vitro, and increased survival duration of the mice when compared to its controls. miR-181a controls osteopontin expression in tumor cells by regulating their proliferation and apoptosis.

MiRNAs can silence a wide range of genes, which may be an advantage for targeting heterogenous tumors like glioblastoma. Osteopontin (OPN) plays both an oncogenic role in a variety of cancers and can immune modulate macrophages. We conducted a genome wide profiling and bioinformatic analysis to identify miR-181a/b/c/d as potential miRNAs that target OPN. Luciferase assays confirmed the binding potential of miRNAs to OPN. Expression levels of miR-181a/b/c/d and OPN were evaluated by using quantitative real-time PCR and enzyme-linked immunosorbent assay in mouse and human glioblastomas and macrophages that showed these miRNAs were downregulated in Glioblastoma associated CD11b+ cells compared to their matched blood CD14b+ cells. miRNA mimicking and overexpression using lentiviruses showed that MiR-181a overexpression in glioblastoma cells led to decreased OPN production and proliferation and increased apoptosis in vitro. MiR-181a treatment of immune competent mice bearing intracranial glioblastoma demonstrated a 22% increase in median survival duration relative to that of control mice.

• cancer stem cells
• glioblastoma
• glioblastoma-infiltrating macrophages (GIMs)
• macrophages
• miRNA, miR-181
• microRNAs
• osteopontin
• osteopontin (OPN)
• reverse transcription polymerase chain reaction (RT-PCR)

• CA120813 NIH HHS
• P50 CA127001 NIH HHS

Differential expression of miRNA provides important insights into pathogenesis of cancer including leukemia. Deregulation of microRNA may contribute to hematopoietic malignancies. In this study, we aimed to evaluate the role of miR-181a and miR-196b in acute lymphoblastic leukemia (ALL) and correlate their expression with clinical and laboratory data.

The study was performed on bone marrow samples of 70 consecutive newly diagnosed pediatric (ALL) patients, of which 56 were evaluated for both miR-181a and miR-196b (all 70 for miR-181a) by real-time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). In addition, bone marrow from seven age and sex matched healthy controls derived from donors of bone marrow transplantation were assessed.

miR-181a expression was significantly up-regulated in ALL patients compared with healthy controls (p<0.001). However, miR-196b expression was significantly down-regulated in patients compared with healthy controls (p=0.038).

Our results suggest that miR-181a has an oncogenic, while miR-196b has a tumor suppressive role in pediatric ALL patients. A finding which demonstrate the potential role of these microRNAs in pathogenesis of pediatric ALL. Also, estimation of their expression level may provide a tool for confirmation of a diagnosis of childhood ALL and could be a possible predictor of early relapse.

• ALL
• Pediatric
• microRNA-181a
• microRNA-196b

• Breast cancer
• MicroRNA
• Pathogenesis
• Therapy

• Heroin addiction
• biomarker
• diagnosis
• hsa-miR-181a
• substance abuse

• Biomarkers
• Exosomes
• Gliomas
• MicroRNAs
• Proteins
• Therapy
• pathogenesis

Hypoxic ischemic encephalopathy (HIE) is the most frequent cause of acquired infant brain injury. Early, clinically relevant biomarkers are required to allow timely application of therapeutic interventions. We previously reported early alterations in several microRNAs (miRNA) in umbilical cord blood at birth in infants with HIE. However, the exact timing of these alterations is unknown. Here, we report serial changes in six circulating, cross-species/bridging biomarkers in a clinically relevant porcine model of neonatal HIE with functional analysis. Six miRNAs—miR-374a, miR-181b, miR-181a, miR-151a, miR-148a and miR-128—were significantly and rapidly upregulated 1-h post-HI. Changes in miR-374a, miR-181b and miR-181a appeared specific to moderate-severe HI. Histopathological injury and five miRNAs displayed positive correlations and were predictive of MRS Lac/Cr ratios. Bioinformatic analysis identified that components of the bone morphogenic protein (BMP) family may be targets of miR-181a. Inhibition of miR-181a increased neurite length in both SH-SY5Y cells at 1 DIV (days in vitro) and in primary cultures of rat neuronal midbrain at 3 DIV. In agreement, inhibition of miR-181a increased expression of BMPR2 in differentiating SH-SY5Y cells. These miRNAs may therefore act as early biomarkers of HIE, thereby allowing for rapid diagnosis and timely therapeutic intervention and may regulate expression of signalling pathways vital to neuronal survival.

• BMP signalling
• Biomarker
• Hypoxic ischemic encephalopathy
• Piglet model
• miR-181a
• miRNA