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MicroRNA (miRNA), functioning as a post-transcriptional regulatory element, plays a significant role in numerous regulatory mechanisms and serves as a crucial intrinsic factor influencing axon regeneration. Prior investigations have elucidated the involvement of miRNA-9 in various processes, however, its specific contribution to axon regeneration in the central nervous system (CNS) remains uncertain. Hence, the zebrafish Mauthner axon regeneration model was employed to manipulate the expression of miRNA-9 in single cells, revealing that upregulation of miRNA-9 facilitated axon regeneration. Additionally, her6, a downstream target gene of miRNA-9, was identified as a novel gene associated with axon regeneration. Suppression of her6 resulted in enhanced Mauthner axon regeneration, as evidenced by the significantly improved regenerative capacity observed in her6 knockout zebrafish. In addition, modulation of her6 expression affects intracellular calcium levels in neurons and promoting her6 expression leads to a decrease in calcium levels in vivo using the new NEMOf calcium indicator. Moreover, the administration of the neural activity activator, pentylenetetrazol (PTZ) partially compensated for the inhibitory effect of her6 overexpression on the calcium level and promoted axon regeneration. Taken together, our study revealed a role for miRNA-9 in the process of axon regeneration in the CNS, which improved intracellular calcium activity and promoted axon regeneration by inhibiting the expression of downstream target gene her6. In our study, miRNA-9 emerged as a novel and intriguing target in the intricate regulation of axon regeneration and offered compelling evidence for the intricate relationship between calcium activity and the facilitation of axon regeneration.

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Finding a link between a hormone and microRNAs (miRNAs) is of great importance since it enables the adjustment of genetic composition or cellular functions without needing gene-level interventions. The dicer-mediated cleavage of precursor miRNAs is an interface link between miRNA and its regulators; any disruption in this process can affect neurogenesis. Besides, the hormonal regulation of miRNAs can occur at the molecular and cellular levels, both directly, through binding to the promoter elements of miRNAs, and indirectly, via regulation of the signaling effects of the post-transcriptional processing proteins. Estrogenic hormones have many roles in regulating miRNAs in the brain. This review discusses miRNAs, their detailed biogenesis, activities, and both the general and estrogen-dependent regulations. Additionally, we highlight the relationship between miR-29, miR-9, and estrogens in the nervous system. Such a relationship could be a possible etiological route for developing various neurodegenerative disorders.

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MicroRNAs (miRNAs) are a class of non-coding small RNAs with about 22 nucleotides in eukaryotes. They regulate gene expression at the post-transcriptional level and play a key role in physiological and pathological processes. As one of the most abundant miRNAs in the human brain, miRNA-9 (miR-9) has attracted extensive attention due to its important role in the maintenance of normal function of the nervous system and the occurrence and development of nervous system diseases. Hence, we reviewed the neuroprotective effect of miR-9 in neurological diseases. MiR-9 may be a potential target of nervous system diseases.

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Our previous research found that FOXO1 aggravates the mucosal barrier injury in inflammatory bowel disease (IBD) by regulating TLR4/MD2 signaling. In this study, we further reveal the mechanism of action whereby miRNA-9a-5p inhibits the mucosal barrier injury after regulating FOXO1. An IBD model was established in C57BL/6N mice using dextran sulfate sodium (DSS). The effects of endogenous miRNA-9a-5p were mimicked/antagonized by intraperitoneally injecting miRNA-9a-5p agomir and antagomir. Body weights of mice were monitored and the disease activity index scores were assessed. H&E staining was performed to examine pathological changes, while immunohistochemical (IHC) staining was conducted to measure the expressions of TJ proteins (ZO-1, Occludin), as well as FOXO1 and TLR4. The mucosal permeability was assessed by FITC-D, the tissue inflammatory cytokines were detected by enzyme linked immunosorbent assay, and the expressions of ZO-1 and Occludin were measured through Western blot analysis. Caco-2 cells were cultured in vitro to establish a monolayer model of the mucosal barrier. TNF-α was used to induce the cell damage, while agomir and antagomir were transfected to mimic/antagonize the miRNA-9a-5p action, followed by determination of barrier permeability. There was a targeted regulatory relationship between MiRNA-9a-5p and FOXO1. MiRNA-9a-5p could suppress the FOXO1 expression, thereby downregulating the TLR4 signaling activation, inhibiting the mucosal barrier injury, and elevating the expressions of TJ proteins. We also found in Caco-2 cells that miRNA-9a-5p could protect cells from inflammatory injury and reduce permeability. In rescue experiments, the effect of agomir was found inhibited by the overexpression of FOXO1 in agomir-treated cells. This study found that miRNA-9a-5p could inhibit the TLR4 signaling activation by targeting FOXO1, thereby exerting a protective effect on the mucosal barrier injury in IBD.

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MicroRNAs (miRNAs) are regulatory RNA molecules that bind to target messenger RNAs (mRNAs) and affect the stability or translational efficiency of the bound mRNAs. Single or dual-luciferase reporter systems have been successfully used to identify miRNA target genes in mammalian cells. These reporter systems, however, are not sensitive enough to verify miRNA-target gene relationships in insect cell lines because the promoters of the target luciferase (usually Renilla) used in these reporter systems are too weak to drive sufficient expression of the target luciferase in insect cells. In this study, we replaced the SV40 promoter in the psiCHECK-2 reporter vector, which is widely used with mammalian cell lines, with the HSV-TK or AC5.1 promoter to yield two new dual-luciferase reporter vectors, designated psiCHECK-2-TK and psiCHECK-2-AC5.1, respectively. Only psiCHECK-2 and psiCHECK-2-AC5.1 had suitable target (Renilla)/reference (firefly) luciferase activity ratios in mammalian (HeLa and HEK293) and insect (Sf9, S2, Helicoverpa zea fat body and ovary) cell lines, while psiCHECK-2-TK had suitable Renilla/firefly luciferase activity ratios regardless of the cell line. Moreover, psiCHECK-2-TK successfully detected the interaction between Helicoverpa armigera miRNA9a and its target, the 3'-untranslated region of heat shock protein 90, in both mammalian and H. zea cell lines, but psiCHECK-2 failed to do so in H. zea cell lines. Furthermore, psiCHECK-2-TK with the target sequence, HzMasc (H. zea Masculinizer), accurately differentiated between H. zea cell lines with or without the negative regulation factor (miRNA or piRNA) of HzMasc. These data demonstrate that psiCHECK-2-TK can be used to functionally characterize small RNA target genes in both mammalian and insect cells.

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Neurotrophin receptors regulate neuronal survival and network formation, as well as synaptic plasticity in the brain via interaction with their ligands. Here, we examined early changes in the expression of neurotrophin receptor genes Ntk1 (TrkA), Ntrk2 (TrkB), Ntrk3 (TrkC), Ngfr (p75NTR) and miRNAs that target theses gens in the mouse brain after induction of seizure activity by pentylenetetrazol. We found that expression of Ntrk3 and Ngfr was upregulated in the cortex and the hippocampus 1-3 hours after the seizures, while Ntrk2 expression increased after 3-6 hours in the anterior cortex and after 1 and 6 hours in the hippocampus. At the same time, the ratio of Bcl-2/Bax signaling proteins increased in the anterior and posterior cortex, but not in the hippocampus, suggesting the activation of anti-apoptotic signaling. Expression of miRNA-9 and miRNA-29a, which were predicted to target Ntrk3, was upregulated in the hippocampus 3 hours after pentylenetetrazol injection. Therefore, early cellular response to seizures in the brain includes induction of the Ntrk2, Ntrk3, Ngfr, miRNA-9, and miRNA-29a expression, as well as activation of Bcl-2 and Bax signaling pathways, which may characterize them as important mediators of neuronal adaptation and survival upon induction of the generalized brain activity.

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BACKGROUND: Psoriasis is a chronic skin disorder manifested by recurrent episodes of scaly, red, itchy skin patches that occur within apparently normal skin. OBJECTIVES: This study was performed to detect the expression of serum and tissue (lesion and non-lesion) LncRNA MALAT-1 and MiRNA-9 that might be used as biomarkers for psoriasis. METHODS: Blood samples were obtained from 60 psoriasis patients and 40 controls, as well as 4 mm punch biopsy from lesional and non lesional skin of psoriatic patient and normal skin of healthy controls. Expression of LncRNA MALAT-1 and miRNNA-9 in serum and tissues was detected by real time qRT-PCR. RESULTS: a statistically significant increase in the expression of MALAT-1 in lesional and non-lesional skin and serum of psoriatic patients in comparison to controls were detected. Moreover, there was statistically significant increase in serum MiRNA-9 in patients in comparison to controls, while its tissue level was significantly lower in patients. CONCLUSION: This study highlights the dysregulation of LncRNA MALAT-1 and miRNA-9 in psoriasis. Elevated expression of MALAT-1 in lesional skin of psoriatic patients compared to non-lesional skin may possibly contribute to the development of psoriatic plaques.

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OBJECTIVE: Molecular markers for the detection of breast cancer and its different types, grades, and stages lack enough sensitivity and specificity. This study evaluates the expression of miRNAs 9 and 342 in sera of different types, grades, and stages of BC. Moreover, the assessment of their sensitivity, specificity, diagnostic, and prognostic role in detecting different types of BC. METHODS: Blood was collected from 200 females outpatients, divided into five groups each 40 subjects: control, benign breast tumor, estrogen receptor (ER+)/progesterone receptor (PR+) BC, human epidermal growth factor receptor (HER+) BC, and triple-negative BC. BC subjects were further subdivided according to grade and stage. Expressions of miRNAs 9 and 342 were measured for all subjects by real-time polymerase chain reaction (RT-PCR). RESULTS: Results showed that serum expression of both miRNAs 9 and 342 can be used for the diagnosis of different types of BC. Their expression can be used to significantly differentiate between different grades and stages of BC. MiRNAs 9 and 342 showed high sensitivity of 92.5% and specificity of (81.2 and 88.7%), respectively, for triple-negative BC. CONCLUSION: The expressions of miRNAs 9 and 342 provide potential roles as serological biomarkers for the diagnosis and prognosis of different types, grades, and stages of BC.

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Spinal cord ischemia-reperfusion injury (SCII) is still a serious problem, and the mechanism is not fully elaborated. In the rat SCII model, qRT-PCR was applied to explore the altered expression of miR-9 (miR-9a-5p) after SCII. The biological function of miR-9 and its potential target genes based on bioinformatics analysis and experiment validation in SCII were explored next. Before the surgical procedure of SCII, miR-9 mimic and inhibitor were intrathecally infused. miR-9 mimic improved neurological function. In addition, miR-9 mimic reduced blood-spinal cord barrier (BSCB) disruption, inhibited apoptosis and decreased the expression of IL-6 and IL-1ß after SCII. Gene Ontology (GO) analysis demonstrated that the potential target genes of miR-9 were notably enriched in several biological processes, such as "central nervous system development", "regulation of growth" and "response to cytokine". The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the potential target genes of miR-9 were significantly enriched in several signaling pathways, including "Notch signaling pathway", "MAPK signaling pathway", "Focal adhesion" and "Prolactin signaling pathway". We further found that the protein expression of MAP2K3 and Notch2 were upregulated after SCII while miR-9 mimic reduced the increase of MAP2K3 and Notch2 protein. miR-9 mimic or MAP2K3 inhibitor reduced the release of IL-6 and IL-1ß. miR-9 mimic or si-Notch2 reduced the increase of cleaved-caspase3. Moreover, MAP2K3 inhibitor and si-Notch2 reversed the effects of miR-9 inhibitor. In conclusion, overexpression of miR-9 improves neurological outcomes after SCII and might inhibit BSCB disruption, neuroinflammation, and apoptosis through MAP2K3-, or Notch2-mediated signaling pathway in SCII.

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BACKGROUND: To investigate the mechanism of microRNA9 in inhibiting proliferation and migration of lung squamous cell carcinoma cells via neuron-restricted silencing factor/epidermal growth factor receptor. MATERIAL AND METHODS: Detection of microRNA9, neuron-restricted silencing factor, and epidermal growth factor receptor expression levels in lung cancer patients' tissues and lung cancer cells by Western blotting and quantitative polymerase chain reaction. Detection of cell proliferation by colony formation assay and cell counting kit-8 assay. Detection of cell migration by wound-healing assay and Transwell assay. And detection of the regulatory effect between neuron-restricted silencing factor and epidermal growth factor receptor by Luciferase reporter gene system. Subcutaneous implantation mouse models of NCI-H520 cells were constructed to detect cell proliferation in vivo, and Kaplan-Meier method calculated patient survival. RESULTS: The expression of microRNA9 and epidermal growth factor receptor was higher in lung cancer tissues than in normal lung tissues, while the expression of neuron-restricted silencing factor was lower in lung cancer tissues than in normal lung tissues. MicroRNA9 higher expression was strongly related to tumor size, and TNM stage and predicted showed reduced overall survival in patients with lung cancer. Further loss of function and enhancement experiments revealed that inhibition of microRNA9 could significantly inhibit lung squamous carcinoma cell proliferation and migration. Luciferase reporter assay demonstrated that microRNA9 could bind to NRSF messenger RNA and inhibit its expression, neuron-restricted silencing factor overexpression also exerted inhibitory effects on cell proliferation and migration. Moreover, Luciferase reporter assay showed that neuron-restricted silencing factor downregulate epidermal growth factor receptor expression levels by binding to epidermal growth factor receptor promoter regions, and Pearson's correlation analysis indicated that the levels of microRNA9 in lung cancer tissues were correlated with neuron-restricted silencing factor and epidermal growth factor receptor. Combined microRNA9 with neuron-restricted silencing factor or epidermal growth factor receptor to predict the prognosis of patients with lung cancer may be more accurate. CONCLUSION: MicroRNA9 inhibits proliferation and migration of lung squamous cell carcinoma cells by inhibiting neuron-restricted silencing factor/epidermal growth factor receptor axis. MicroRNA9 can be a new prognostic marker and therapeutic target for lung squamous cell carcinoma.

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BACKGROUND: Large amounts of researches indicate that non-coding RNAs play a crucial role in many malignancies. However, the potential mechanisms of non-coding RNAs involved in osteosarcoma tumorigenesis remain elusive. MATERIALS AND METHODS: The expression of long non-protein coding RNA 691 (lncRNA 691) in cell lines and paired osteosarcoma tissues was compared by qRT-PCR assay. Then, we explored the tumor suppressor function of lncRNA 691 with MTS and colony formation assay. Flow cytometry results showed lncRNA 691 can enhance cell apoptosis. Then, we predicted and verified the negative regulation relationship with miRNA and the miRNA's target gene. Lastly, we revealed the tumorigenesis function of lncRNA-691/miRNA/target gene axis in osteosarcoma. RESULTS: In our study, we disclosed that lncRNA 691 had low expression levels in osteosarcoma cell lines and tissues. Overexpression of lncRNA 691 could suppress the cell proliferation and induce cell apoptosis in MG-63 cell line. Then, bioinformatics analyses were performed and miR-9-5p was found to negatively regulate the lncRNA 691 expression and promote the osteosarcoma tumorigenesis in vitro. PTEN was predicted as the target gene of miR-9-5p. Luciferase reporter assay and RIP assay demonstrated the regulatory network of lncRNA 691/miR-9-5p/PTEN. We revealed that PTEN was downregulated by the overexpression of miR-9-5p and upregulated by the overexpression of lncRNA 691. At last, the apoptosis-associated protein of the lncRNA 691/miR-9-5p/PTEN/PI3K/AKT was further demonstrated. CONCLUSION: LncRNA 691/miR-9-5p could regulate the tumorigenesis by regulating the PTEN/PI3K/AKT signal pathway in osteosarcoma.

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The chronic consumption of alcohol causes a worsening of the events that follow the cerebral ischemia. These events are regulated through the expression of several genes and microRNAs. The aimof this work was To analyze and describe the expression profile of PARP and AIF and miRNA-9 proteins in rats submitted to focal cerebral ischemia, associated or not with chronic alcoholism model. Methods: Twenty adult Wistar rats, subdivided into: control; ischemic; alcoholic and ischemic / alcoholized for immunohistochemical analysis and miRNA-9 gene expression. Results: There was a reduction in the protein expression of PARP-1 and a positive marking for AIF in the ischemic / alcoholized group. The miRNA-9 did not obtain significant expression. The association of ischemia with chronic alcohol use promoted a tendency to low expression of miRNA-9, low expression of PARP-1 and high expression of AIF, indicating an interference in the protective effect of miRNA-9 be observed in the other groups.

El consumo crónico de alcohol provoca un empeoramiento de los eventos que siguen a la isquemia cerebral. Estos eventos están regulados a través de la expresión de varios genes y microRNA. El objetivo de este trabajo fue analizar y describir el perfil de expresión de las proteínas PARP y AIF y microRNA-9 en ratas sometidas a isquemia cerebral focal, asociadas o no, con el modelo de alcoholismo crónico. Veinte ratas Wistar adultas se dividieron en: grupo control, isquémico alcohólico, e isquémico / alcoholizado para análisis inmunohistoquímico y expresión de genes microRNA-9. Resultados: Hubo una reducción en la expresión de proteínas de PARP-1 y un marcado positivo para AIF en el grupo isquémico / alcoholizado. No se observó una expresión significativa en el microRNA-9. La asociación de la isquemia con el consumo crónico de alcohol promovió una tendencia a la baja expresión de microRNA-9, baja expresión de PARP1 y alta expresión de AIF, lo que indica una interferencia en el efecto protector de microRNA-9 en los otros grupos.

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A pro-inflammatory cytokine, IL-17A, is associated with increased risk of developing numerous cancers, including non-small cell lung cancer (NSCLC). IL-17A is a target gene for miR-9. This encouraged us to analyze these two genes in terms of their usefulness as prognostic markers in NSCLC. The expression levels of IL-17A gene and miR-9 was assessed in 26 NSCLC tissue samples and 26 unchanged lung tissue adjacent to lung tumors (control tissue), using qPCR. In both tissue groups, a decreased expression of IL-17A was observed in 100% of samples. Increased expression of miRNA-9 was observed in 92% of tumor samples, and in 100% of control samples. Neither statistical differences in the level of expression IL-17A depending on the patient's age, gender, smoking status, nor histopathology of the cancer was found. Regarding the presence of nodule metastasis ('N' value in TNM classification), significantly lower expression level of IL-17A was observed in cN2 as compared with cN1 group. Additionally, statistically lower IL-17A expression was found in III versus II tumor stage (cAJCC classification). Significant negative correlation between both studied genes was revealed in SCC subgroup. This leads to the conclusion that miRNA-9 can regulate the expression of IL-17A as an IL-17A mRNA antagonistic mediator. Inhibition of proinflammatory action of IL-17A in correlation with tumor progression can be related to various activity of Th17 cells on cancer development according to its immunogenicity, and also may suggest suppressive role of IL-17A in tumor progression. However, because of low number of analyzed samples, further studies on the functional role of IL-17A in development and/or progression NSCLC seem warranted.

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Hypertension is a universal risk factor for a variety of cardiovascular diseases. Investigation of the mechanism for hypertension will benefit around 40% of the world's adult population. MicroRNA is crucial for the initiation and progression of cardiovascular diseases. In this study, angiotensin II-treated human umbilical vein endothelial cells were used as a model to imitate the pathological changes in endothelial cells under hypertensive conditions. We demonstrated that microRNA-9 (miR-9) suppressed angiotensin II-induced apoptosis and enhanced proliferation in human umbilical vein endothelial cells. Direct interaction between miR-9 and mitochondria associated membrance domain containing glycosylphosphatidylinositol anchor 2 (MDGA2) was determined. Moreover, miR-9 suppressed MDGA2 levels by binding to the 3' UTR site of the MDGA2 gene. This negative regulation of MDGA2 by miR-9 significantly increased proliferation and decreased apoptosis. Re-introduction of MDGA2 in the miR-9 overexpressed human umbilical vein endothelial cells and normalized proliferation, apoptosis, and the cell cycle. In summary, the present study demonstrated miR-9 inhibited expression of MDGA2 leading to the inhibition of apoptosis and promotion of proliferation in angiotensin II-treated human umbilical vein endothelial cells.

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Disruptions in multiple neurobiological pathways and neuromolecular processes have been widely implicated in the etiopathology of Alzheimer's disease (AD), a complex, progressive, and ultimately lethal neurological disorder whose current incidence, both domestically and globally, is reaching epidemic proportions. While only a few percent of all AD cases appear to have a strong genetic or familial component, the major form of this disease, known as idiopathic or sporadic AD, displays a multi-factorial pathology and represents one of the most complex and perplexing neurological disorders known. More effective and innovative pharmacological strategies for the successful intervention and management of AD might be expected: (i) to arise from strategic-treatments that simultaneously address multiple interrelated AD targets that are directed at the initiation, development, and/or propagation of this disease and (ii) those that target the "neuropathological core" of the AD process at early or upstream stages of AD. This "Perspectives paper" will review current research involving microRNA (miRNA)-mediated, messenger RNA (mRNA)-targeted gene expression pathways in sporadic AD and address the potential implementation of evolving anti-microRNA (AM) strategies in the amelioration and clinical management of AD. This novel-therapeutic approach: (i) incorporates a system involving the restoration of multiple miRNA-regulated mRNA-targets via the use of selectively-stabilized AM species; and (ii) that via implementation of synthetic AMs, the abundance of only relatively small-families of miRNAs need be modulated or neutralized to re-establish neural-homeostasis in the AD-affected brain. In doing so, these strategic approaches will jointly and interactively address multiple AD-associated processes such as the disruption of synaptic communication, defects in amyloid peptide clearance and amyloidogenesis, tau pathology, deficits in neurotrophic support, alterations in the innate immune response, and the proliferation of neuroinflammatory signaling.

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The irrefutable change in the expression of brain-enriched microRNAs (miRNAs) following ischemic stroke has promoted the development of radical miRNA-based therapeutics encompassing neuroprotection and neuronal restoration. Our previous report on the systems-level prediction of miR-9 in post-stroke-induced neurogenesis served as a premise to experimentally uncover the functional role of miR-9 in post-ischemic neuronal survival and regeneration. The oxygen-glucose deprivation (OGD) in SH-SY5Y cells significantly reduced miR-9 expression, while miR-9 mimic transfection enhanced post-ischemic neuronal cell viability. The next major objective involved the execution of a drug repositioning strategy to augment miR-9 expression via structure-based screening of Food and Drug Administration (FDA)-approved drugs that bind to Histone Deacetylase 4 (HDAC4), a known miR-9 target. Glucosamine emerged as the top hit and its binding potential to HDAC4 was verified by Molecular Dynamics (MD) Simulation, Drug Affinity Responsive Target Stability (DARTS) assay, and MALDI-TOF MS. It was intriguing that the glucosamine treatment 1-h post-OGD was associated with the increased miR-9 level as well as enhanced neuronal viability. miR-9 mimic or post-OGD glucosamine treatment significantly increased the cellular proliferation (BrdU assay), while the neurite outgrowth assay displayed elongated neurites. The enhanced BCL2 and VEGF parallel with the reduced NFκB1, TNF-α, IL-1ß, and iNOS mRNA levels in miR-9 mimic or glucosamine-treated cells further substantiated their post-ischemic neuroprotective and regenerative efficacy. Hence, this study unleashes a potential therapeutic approach that integrates neuronal survival and regeneration via small-molecule-based regulation of miR-9 favoring long-term recovery against ischemic stroke.

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PURPOSE: MicroRNAs are involved in diverse biological processes and their dysregulation is a common event in various diseases including breast cancer. Breast cancer is a major threat to women's health. This study was designed to examine the expression levels of miR-9 and miR-34a in breast tumor tissue samples and plasma of breast cancer patients, compare their expression pattern between tissue samples and plasma samples of patients and analyze their relationship with tumor clinical features. Also, the potential of these miRNAs as diagnostic biomarkers for breast cancer was investigated. MATERIALS AND METHODS: The expression levels of miR-9, miR-34a and CDH1 were measured by real-time reverse transcription polymerase chain reaction and ΔΔct method. Data were analyzed using t-test and one-way ANOVA. The sensitivity and specificity of miRNAs were determined by receiver operating characteristic (ROC) curve. RESULTS AND DISCUSSION: The expression levels of miR-9 and miR-34a were significantly down-regulated in tumor tissues compared to healthy tissues (fold change = 0.26, p = 0.0051 for miR-9 and fold change = 0.55, p = 0.021 for miR-34a). While no significant difference was observed in the expression levels of miR-9 (p = 0.205) and miR-34a (p = 0.132) in plasma samples of patients compared to normal plasma. CDH1 expression in tumor tissue was not significantly different from normal tissue (p = 0.33). We found that expression level of miR-9 in patients with tumor size larger than 5 cm (p = 0.026) and expression level of miR-34a in patients with higher stage (lll & lV, p = 0.03) were significantly down-regulated. Also miR-34a expression level was positively correlated with patient's age (p = 0.03). CONCLUSION: According to the ROC curves, the area under the curve (AUC) of miR-9 in tissue was 0.71 (p = 0.009) with sensitivity 83.33% and specificity 70.37%. The AUC for miR-34a in tissue was 0.72 (p = 0.007) with sensitivity 72% and specificity 76%. Thus miR-9 and miR-34a have the capability for distinguishing tumor tissues from healthy tissues and the study of their expression levels in tissue may be used as a biomarker for the diagnosis of breast cancer patients from healthy women.

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