miR-153 Levels Research Articles

Association of Serum Extracellular Vesicle miRNAs with Cognitive Functioning and Quality of Life in Parkinson's Disease.

The identification of mechanisms associated with Parkinson disease (PD) development in cognitive functioning would be of great usefulness to clarify PD pathogenesis and to develop preventive and therapeutic strategies. In this study, blood serum extracellular vesicle (EV) levels of the candidate microRNAs (small noncoding RNAs that play a role in gene expression regulation):,miR-7, miR-21, miR-153, miR-155, miR-200a and miR-214, have been investigated for association with PD in a group of 93 patients with cognitive parameters, PD symptoms, affected quality of life and some clinical characteristics. MiRNA was extracted from patients' blood serum EVs, transcribed into cDNA and their expression was evaluated using RT-PCR. The miR-153 and miR-200a showed the most plausible correlations with cognitive functioning parameters such as general intellectual functioning, psychomotor speed, mental flexibility, and nonverbal executive functions. Moreover, lower levels of miR-153 were associated with attention span, working memory and psychomotor speed with learning. Increased levels of miR-200a, miR-7, miR-214, and miR-155 were also linked with neurological functioning, such as bradykinesia, tremor, balance and others. Despite the fact that due to small sample size, our results should be considered as preliminary, our study suggests that miRNA expression in EVs could be associated with symptom severity, cognitive impairment and quality of life in PD.

MiR-153 is Involved in Testicular Ischemia/Reperfusion Injury by Directly Targeting FOXO3 and Regulating Spermatogonia Pyroptosis.

IRI often occurs after detorsion of testicular torsion, which can contribute to permanent damage to sperm production function due to spermatogonia pyroptosis. Mounting data manifestthat miRNAs possessa functionin the IRI progression.However, the miR-153 function in testicular IRI remains unclear. We aim to elucidate the regulatory mechanism of miR-153 in regulating spermatogonia pyroptosis in testicular IRI. We developed the mouse testicular torsion/detorsion (T/D) model and the oxygen-glucose deprivation/reperfusion (OGD/R) model to examine themiR-153 functionin testicular IRI.The extent of testicular ischemic damage was evaluated through HE staining the testicular tissue. Various experimental methods, including Western blotting, QRT-PCR, MDA, SOD assays, and immunohistochemistry (IHC), were deployed to examine the miR-153 levels and the generation of ROS in the testicular tissues. Furthermore, we determined the FoxO3 levels and pyroptosis-related proteins in GC-1 cells. Cell viability was assessed using the CCK-8 assay. Finally, the connection between miR-153 and FoxO3 was verifiedby employingdual luciferase reporter gene assays and Ago2-RIP. In the testicular IRI, we noted a significant elevation in the pyroptosis-correlated proteins NLRP3, caspase-1 (CASP1), IL-1β, and IL-18 levels. Furthermore, we noted a significant upregulation of miR-153 in the IRI testicular tissues and GC-1 cells treated with OGD/R, and the miR-153 upregulation increased cell pyroptosis. Conversely, the miR-153 downregulation and FoxO3 overexpression reduced cell pyroptosis. Subsequently, we validated that FoxO3 is a miR-153 target gene. During the OGD/R process, miR-153 increased cell pyroptosis in GC-1 cells by suppressing the FoxO3 expression. We identified that the regulation of testicular IRI-induced cell pyroptosis is mediated by miR-153 via its targeting of FoxO3.

Cellular microRNAs target SARS-CoV-2 spike protein and restrict viral replication.

MicroRNAs (miRNAs) regulate gene expression post-transcriptionally and are implicated in viral replication and host tropism. miRNAs can impact the viruses either by directly interacting with the viral genome or modulating host factors. Although many miRNAs have predicted binding sites in the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) viral RNA genome, little experimental validation has been done. We first identified 492 miRNAs that have binding site(s) on the spike (S) viral RNA by a bioinformatics prediction. We then validated the selected 39 miRNAs by examining S-protein levels after co-expressing the S-protein and a miRNA into the cells. Seven miRNAs were found to reduce the S-protein levels more than 50%. Among them, miR-15a, miR-153, miR-298, miR-508, miR-1909 and miR-3130 also significantly reduced SARS-CoV-2 viral replication. SARS-CoV-2 infection decreased the expression levels of miR-298, miR-497, miR-508, miR-1909, and miR-3130, but had no significant effects on miR-15a and miR-153 levels. Intriguingly, the targeting sequences of these miRNAs on the S viral RNA showed sequence conservation among the variants of concern. Our results suggest that these miRNAs elicit effective antiviral defense against SARS-CoV-2 by modulating S-protein expression and are likely targeting all the variants. Thus, the data signifies the therapeutic potential of miRNA-based therapy for SARS-CoV-2 infections.

MiR-153 Targets Autophagy and Apoptosis Caspase Family to Explore the Molecular Mechanism of Polystyrene Nanoparticles Intervening in Thoracoabdominal Aortic Aneurysm

This study investigates whether miR-153 regulates the expression of autophagy and apoptosis-related gene Caspase3, and analyzes the role of polystyrene nanoparticles in thoracoabdominal aortic aneurysm cells. Surgically resected thoracoabdominal aortic aneurysm tissue samples were included as the observation group and the control group included 2 cm tissues from the side of thoracoabdominal aortic aneurysm. The mRNA levels of miR-153 and Caspase3 were assessed by reverse transcription polymerase chain reaction (RT-PCR) and cell proliferation, apoptosis, invasion, and migration were evaluated. Tissue microarray and RT-PCR showed that miR-153 was expressed in tissues and it displayed a targeted relationship with Caspase3. Transwell results showed that transfection of miR-153-targeted Caspase3 nanoparticles significantly reduced the infiltration of thoracic and aortic aneurysm. After si-RNA interfered with the expression of miR-153, the proliferation rate of thoracoabdominal aortic aneurysms in the miR-153-targeted Caspase3-directed nanoparticle group was significantly reduced. On the contrary, when miR-153 was overexpressed, the apoptosis was significantly reduced. Transfection of si-miR-153-targeting Caspase3 nanoparticles significantly reduced the invasion and metastasis ability of thoracoabdominal aortic aneurysm cells and the migration ability was increased after reversing miR-153 expression. The decreased expression of miR-153 is related to the increased expression of Caspase3 and enhanced invasion and metastasis of thoracoabdominal aortic aneurysms. Overexpression of miR-153 can inhibit the expression of Caspase3 and targeted nanoparticles can effectively enhance cell activities.

MicroRNA‑153 may act as a potential biomarker and prognostic indicator of patients with gastric cancer.

MicroRNA (miR/miRNA)-153, as a novel tumor-related miRNA, has been found to be aberrantly expressed in different types of cancer; however, to the best of our knowledge, the role of miR-153 in gastric cancer (GC) remains unclear. The present study demonstrated that miR-153 expression was markedly decreased in GC, including GC cell lines and culture medium, GC tissues, and serum samples, based on reverse transcription-quantitative PCR, and this was further confirmed by fluorescence in situ hybridization. Transfection with miR-153 mimics inhibited proliferation and migration, and promoted apoptosis in GC cells. The serum expression levels of miR-153 were decreased in 59 patients with GC compared with those of 9 healthy controls, and more decreased in advanced GC compared with early-stage GC, suggesting that miR-153 was associated with tumor progression. Furthermore, serum miR-153 was expressed at significantly lower levels in patients with GC with larger tumor size (≥4 cm; P=0.013), poor differentiation and signet histology (P=0.013), lymph node metastasis (P=0.025) and advanced tumor stage (TNM stage III and IV; P=0.048) compared with patients with a smaller tumor size (<4 cm), well and moderate differentiation, no lymph node metastasis, and TNM stage I and II, respectively. In conclusion, the present study revealed that low miR-153 expression was associated with poor prognosis in GC and miR-153 may potentially act as a tumor biomarker and therapeutic target in GC.

The potential of miR-153 as aggressive prostate cancer biomarker.

Prostate cancer (PC) is one of the most frequently diagnosed cancers in males. MiR-153, as a member of the microRNA (miRNA) family, plays an important role in PC. This study aims to explore the expression and possible molecular mechanisms of the miR-153 action. Formalin-fixed paraffin-embedded (FFPE) tissues were collected from prostatectomy specimens of 29 metastatic and 32 initial stage PC patients. Expression levels of miR-153 were measured using real-time reverse transcription polymerase chain reaction (qRT-PCR). 2-ΔΔCT method was used for quantitative gene expression assessment. The candidate target genes for miR-153 were predicted by TargetScan. Mutations in target genes of miR-153 were identified using exome sequencing. Protein-protein interaction (PPI) networks, Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to investigate the potential molecular mechanisms of miR-153 in PC. MiR-153 was significantly up-regulated in PC tissues compared to non-cancerous tissues. The analysis of correlation between the expression level of miR-153 and clinicopathological factors revealed a statistically significant correlation with the stage of the tumor process according to tumor, node, metastasis (TNM) staging system (p=0.0256). ROC curve analysis was used to evaluate the predictive ability of miR-153 for metastasis development and it revealed miR-153 as a potential prognostic marker (AUC=0.85; 95%CI 0.75-0.95; sensitivity=0.72, specificity=0.86)). According to logistic regression model the high expression of miR-153 increased the risk of metastasis development (odds ratios=3.14, 95% CI 1.62-8.49; p-value=0.006). Whole exome sequencing revealed nonsynonymous somatic mutations in collagen type IV alpha 1 (COL4A1), collagen type IV alpha 3 (COL4A3), forkhead box protein O1 (FOXO1), 2-hydroxyacyl-CoA lyase 1 (HACL1), hypoxia-inducible factor 1-alpha (HIF-1A), and nidogen 2 (NID2) genes. Moreover, KEGG analysis revealed that the extracellular matrix-receptor (ECM-receptor) interaction pathway is mainly involved in PC. MiR-153 is up-regulated in PC tissues and may play an important role in aggressive PC by targeting potential target genes.

Dysregulation of a Heme Oxygenase-Synuclein Axis in Parkinson Disease.

α-Synuclein is a key driver of the pathogenesis of Parkinson disease (PD). Heme oxygenase-1 (HO-1), a stress protein that catalyzes the conversion of heme to biliverdin, carbon monoxide and free ferrous iron, is elevated in PD-affected neural tissues and promotes iron deposition and mitochondrial dysfunction in models of the disease, pathways also impacted by α-synuclein. Elevated expression of human HO-1 in astrocytes of GFAP.HMOX1 transgenic mice between 8.5 and 19 months of age elicits a parkinsonian phenotype characterized by nigrostriatal hypodopaminergia, locomotor incoordination and overproduction of neurotoxic native S129-phospho-α-synuclein. Two microRNAs (miRNA) known to regulate α-synuclein, miR-153 and miR-223, are significantly decreased in the basal ganglia of GFAP.HMOX1 mice. Serum concentrations of both miRNAs progressively decline in wild-type (WT) and GFAP.HMOX1 mice between 11 and 18 months of age. Moreover, circulating levels of miR-153 and miR-223 are significantly lower, and erythrocyte α-synuclein concentrations are increased, in GFAP.HMOX1 mice relative to WT values. MiR-153 and miR-223 are similarly decreased in the saliva of PD patients compared to healthy controls. Upregulation of glial HO-1 may promote parkinsonism by suppressing miR-153 and miR-223, which, in turn, enhance production of neurotoxic α-synuclein. The aim of the current review is to explore the link between HO-1, α-synuclein and PD, evaluating evidence derived from our laboratory and others. HO-1, miR-153 and miR-223 and α-synuclein may serve as potential biomarkers and targets for disease-modifying therapy in idiopathic PD.

Plasma miR-153 and miR-223 Levels as Potential Biomarkers in Parkinson's Disease.

BackgroundSmall molecule RNAs (miRNAs) could induce downregulation of α-synuclein (SNCA) expression by binding the 3’ untranslated region of SNCA, thus playing an important role in the pathogenesis of Parkinson’s disease (PD). Recent studies suggest that SNCA-related miRNAs in saliva are promising PD biomarkers. Research on those miRNAs in plasma is rare in patients with PD.ObjectiveTo detect the plasma expression levels of three SNCA related miRNAs (miR-7, miR-153, and miR-223) in PD, and to explore their diagnostic value and associations with clinical phenotype.MethodsMiR-7, miR-153, and miR-223 levels were detected in the plasma of 75 PD patients and 73 normal controls (NCs) via real-time quantitative polymerase chain reaction. The receiver operating characteristic (ROC) curves were delineated to evaluate their diagnostic value in PD. In addition, their associations with demographic, key motor, and non-motor symptoms were explored by serial scales.ResultsThe expression levels of plasma miR-153 and miR-223 were significantly decreased in patients with PD relative to NCs. The area under the ROC curve separating PD from NCs was 63.1% for miR-153 and 86.2% for miR-223, respectively. The plasma miR-153 level in de novo PD was lower than that in treated patients (p = 0.006), its level increased gradually with disease duration (r = 0.358, p = 0.002) and Unified Parkinson’s Disease Rating Scale Part III score (r = 0.264, p = 0.022). Plasma miR-223 level was decreased in patients with clinical possible rapid eye movement sleep behavior disorder (cpRBD) compared with those without cpRBD (p < 0.001), and its level was negatively associated with RBDSQ score (r = -0.334, p = 0.003). Multiple linear regression analysis revealed that disease duration (p = 0.049) was the independently associated factor of miR-153 level; whereas, RBDSQ (p = 0.009) was related to miR-223 level in PD.ConclusionPlasma miR-153 and miR-223 levels could be potential biomarkers of PD.

Expression of miR-210, miR-137, and miR-153 in Patients with Acute Cerebral Infarction.

Aim To explore the expression levels of miR-210, miR-137, and miR-153 in patients with acute cerebral infarction. Material and Methods. 76 patients with acute cerebral infarction treated in our hospital from April 2016 to October 2017 were enrolled as the observation group. Another 64 normal patients were selected as the control group. The patients were divided into the death and survival groups based on 1-year mortality of patients. qRT-PCR was used to detect the expression of miR-210, miR-137, and miR-153 in the serum of each group. Receiver operating characteristic (ROC) curve was employed to analyze the diagnostic value and predictive value of miR-210, miR-137 and miR-153 death in patients. The correlation between miR-210, miR-137, and miR-153 in the serum of the observation group was analyzed by Pearson's test. Results Levels of miR-210 and miR-137 in the observation group were significantly lower than those in the control group, while levels of miR-153 in the observation group were significantly higher than those in the control group (all P < 0.05). The ROC curve of diagnosis of acute cerebral infarction showed that the area under curve of miR-210 was 0.836, that of miR-137 was 0.843, and that of miR-153 was 0.842. The 1-year survival rate was 71.05%. The 1-year survival of the low-expression group of miR-210 and miR-137 was significantly lower than that of the high-expression group, while the 1-year survival of the low-expression group of miR-153 was significantly higher than that of the high-expression group (all P < 0.05). The ROC curve for predicting death showed that the area under curve of miR-210 was 0.786, that of miR-137 was 0.824, and that of miR-153 was 0.858. Pearson's correlation analysis showed that the expression of miR-210 was positively correlated with that of miR-137, while miR-137 was negatively correlated with that of miR-153 and miR-210 was negatively correlated with that of miR-153. Conclusion miR-210, miR-137, and miR-153 have a certain value in the diagnosis and prediction of 1-year death of acute cerebral infarction and may be potential diagnostic and predictive indicators.

Salivary microR-153 and microR-223 Levels as Potential Diagnostic Biomarkers of Idiopathic Parkinson's Disease.

Parkinson's disease (PD) is the most common movement disorder among adults, affecting 2% of the world population older than 65 years of age. No diagnostic biomarker for routine use in clinical settings currently exists. Dysregulation of microRNAs (miRNAs) has been implicated in various neurodegenerative conditions, including PD. Distinct miRNAs have been demonstrated to be involved in the regulation of α-synuclein, a key player in PD pathogenesis; miR-153 and miR-223 are downregulated in the brain and serum of parkinsonian GFAP.HMOX1 transgenic mice where they directly regulate α-synuclein. To ascertain whether salivary miR-153 and miR-223 are similarly downmodulated in, and may serve as diagnostic biomarkers of, idiopathic PD. Using reverse transcriptase quantitative polymerase chain reaction, miR-153 and miR-223 levels were evaluated in the saliva of 77 non-neurological controls and 83 PD patients. Levels of heme oxygenase-1 and α-synuclein were measured using enzyme-linked immunosorbent assay. Analyses were adjusted by age, sex, medication exposure, disease duration, and relevant comorbidities. Log-transformed expression levels of miR-153 and miR-223 were significantly decreased in the saliva of human PD patients in comparison with nonneurological controls. The miRNA expression levels did not change as a function of disease progression (Hoehn and Yahr staging). The area under the receiver operating characteristic curve separating controls from PD patients was 79% (95% confidence interval, 61%-96%) for miR-153 and 77% (95% confidence interval, 59%-95%) for miR-223. The ratios of miRNAs to oligomeric α-synuclein, total α-synuclein, or heme oxygenase-1 protein did not improve accuracy of the test. Salivary miR-153 and miR-223 levels may serve as useful, noninvasive, and relatively inexpensive diagnostic biomarkers of idiopathic PD. © 2019 International Parkinson and Movement Disorder Society.

Glial HMOX1 expression promotes central and peripheral α-synuclein dysregulation and pathogenicity in parkinsonian mice.

α-Synuclein is a key player in the pathogenesis of Parkinson disease (PD). Expression of human heme oxygenase-1 (HO-1) in astrocytes of GFAP.HMOX1 transgenic (TG) mice between 8.5 and 19 months of age results in a parkinsonian phenotype characterized by neural oxidative stress, nigrostriatal hypodopaminergia associated with locomotor incoordination, and overproduction of α-synuclein. We identified two microRNAs (miR-), miR-153 and miR-223, that negatively regulate α-synuclein in the basal ganglia of male and female GFAP.HMOX1 mice. Serum concentrations of both miRNAs progressively declined in the wild-type (WT) and GFAP.HMOX1 mice between 11 and 19 months of age. Moreover, at each time point surveyed, circulating levels of miR-153 were significantly lower in the TG animals compared to WT controls, while α-synuclein protein concentrations were elevated in erythrocytes of the GFAP.HMOX1 mice at 19 months of age relative to WT values. Primary WT neurons co-cultured with GFAP.HMOX1 astrocytes exhibited enhanced protein oxidation, mitophagy and apoptosis, aberrant expression of genes regulating the dopaminergic phenotype, and an imbalance in gene expression profiles governing mitochondrial fission and fusion. Many, but not all, of these neuronal abnormalities were abrogated by small interfering RNA (siRNA) knockdown of α-synuclein, implicating α-synuclein as a potent, albeit partial, mediator of HO-1's neurodystrophic effects in these parkinsonian mice. Overexpression of HO-1 in stressed astroglia has previously been documented in the substantia nigra of idiopathic PD and may promote α-synuclein production and toxicity by downmodulating miR-153 and/or miR-223 both within the CNS and in peripheral tissues.

MicroRNA-153 suppresses cell invasion by targeting SNAI1 and predicts patient prognosis in glioma.

Glioma is the most common and rapidly progressive type of malignant primary brain tumor in adults. miR-153 plays a major role in many malignancies; nevertheless, few studies have been conducted on glioma. The aim of the present study was to explore the role of miR-153 and SNAI1 on invasion in glioma. Reverse transcription-quantitative PCR was employed to measure the expression levels of miR-153 and SNAI1 mRNA. Transwell assay was utilized to calculate the capacity of invasion. Luciferase report assay was applied to detect whether SNAI1 was a target of miR-153. miR-153 was downregulated in glioma tissues and cells versus paracancerous tissues and normal immortalized gliocyte HEB cells. Transwell assay was used to measure whether a low expression of miR-153 in glioma indicated inhibition of cell invasion. We verified that SNAI1 was a target of miR-153 and had a negative association with miR-153 detected by luciferase reporter assay. Additionally, miR-153 suppressed cell invasive ability by regulating SNAI1 expression, whose partial function was reversed by SNAI1. miR-153 suppressed cell invasion of glioma by directly targeting SNAI1. Thus, miR-153/SNAI1 axis may be a novel target for cervical cancer treatment.

The Effect of Treadmill Exercise on Expression of α-synuclein and miRNA in MPTP Induced-mouse Models of Parkinson’s Disease

PURPOSE The goal of this study was to demonstrate whether treadmill exercise have an effect on the level of α-synuclein and microRNA (miRNA) in striatum of Parkinson’s Disease (PD) induced mouse models. METHODS To induced mouse model of PD, administered to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 25 mg/kg) and Probenecid (250 mg/kg) by intraperitoneal injections, 2 times per week during 5 weeks. The groups were randomly divided into 3 groups: CON (C57BL/6 control, n=7), MPTP-C (MPTP control, n=7), and ME (MPTP+Exercise, n=7) and treadmill exercise was performed for 8 weeks (10 m/min, 60 min/day, 5 days/week). RESULTS The result show that treadmill exercise significantly improved locomotor function in ME group compared with MPTP-C group in rotarod performance test. Moreover, treadmill exercise was significantly increased levels of miR-153 as regulating SNCA mRNA in ME group compared with MPTP-C group. Conversely, treadmill exercise was significantly decreased levels of SNCA mRNA and α-synuclein in ME group compared with MPTP-C group. We also found that treadmill exercise was significantly increased levels of tyrosine hydroxylase in ME group compared with MPTP-C group. CONCLUSIONS Taken together, these results indicated that treadmill exercise could ameliorate pathologic features of PD via regulating miRNA against MPTP induced mouse model of PD. 색인어: 파킨슨질환, 1-메틸-4페닐-1,2,3,6-í ŒíŠ¸ë¼ížˆë“œë¡œí”¼ë¦¬ë”˜, 알파시누클린, í‹°ë¡œì‹ ìˆ˜ì‚°í™”íš¨ì†Œ, íŠ¸ë ˆë“œë°€ìš´ë™ Keywords: Parkinson’s disease, MPTP, α-synuclein, Tyrosine hydroxylase, Treadmill exercise

MicroRNA-153 targeting of KCNQ4 contributes to vascular dysfunction in hypertension.

AimsKv7.4, a voltage-dependent potassium channel expressed throughout the vasculature, controls arterial contraction and is compromised in hypertension by an unknown mechanism. MicroRNAs (miRs) are post-transcriptional regulators of protein production and are altered in disease states such as hypertension. We investigated whether miRs regulate Kv7.4 expression.Methods and resultsIn renal and mesenteric arteries (MAs) of the spontaneously hypertensive rat (SHR), Kv7.4 protein decreased compared with the normotensive (NT) rat without a decrease in KCNQ4 mRNA, inferring that Kv7.4 abundance was determined by post-transcriptional regulation. In silico analysis of the 3′ UTR of KCNQ4 revealed seed sequences for miR26a, miR133a, miR200b, miR153, miR214, miR218, and let-7d with quantitative polymerase chain reaction showing miR153 increased in those arteries from SHRs that exhibited decreased Kv7.4 levels. Luciferase reporter assays indicated a direct targeting effect of miR153 on the 3′ UTR of KCNQ4. Introduction of high levels of miR153 to MAs increased vascular wall thickening and reduced Kv7.4 expression/Kv7 channel function compared with vessels receiving a non-targeting miR, providing a proof of concept of Kv7.4 regulation by miR153.ConclusionThis study is the first to define a role for aberrant miR153 contributing to the hypertensive state through targeting of KCNQ4 in an animal model of hypertension, raising the possibility of the use of miR153-related therapies in vascular disease.

MiR-153 regulates apoptosis and autophagy of cardiomyocytes by targeting Mcl-1.

MicroRNAs (miRs) are a class of important regulators, which are involved in the regulation of apoptosis. Oxidative stress‑induced apoptosis is the predominant factor accounting for cardiac ischemia‑reperfusion injury. miR‑153 has been previously shown to have an antitumor effect in cancer. However, whether miR‑153 is involved in oxidative stress‑induced apoptosis in the heart remains to be elucidated. To this end, the present study used reverse transcription‑quantitative polymerase chain reaction to detect miR-153 levels upon oxidative stress, and evaluated apoptosis, autophagy and expression of critical genes by western blotting. A luciferase assay was also used to confirm the potential target gene. In the present study, it was found that the expression of miR‑153 was significantly increased upon H2O2 stimulation, and the inhibition of endogenous miR‑153 decreased apoptosis. To further identify the mechanism underlying the pro‑apoptotic effect of miR‑153, the present study analyzed the 3'untranslated region of myeloid cell leukemia‑1 (Mcl‑1), and found that Mcl‑1 was potentially targeted by miR‑153. The forced expression of miR‑153 inhibited the expression of Mcl‑1 and luciferase activity, which was reversed by its antisense inhibitor. Furthermore, it was shown that the inhibition of miR‑153 induced autophagy during oxidative stress, and that its effects of autophagy induction and apoptosis inhibition were efficiently abrogated by Mcl‑1 small interferingRNA. In conclusion, the results of the present study elucidated a novel mechanism by which miR‑153 regulates the survival of cardimyocytes during oxidative stress through the modulation of apoptosis and autophagy. These effects may be mediated directly by targeting Mcl‑1. These finding revealed the potential clinical value of miR‑153 in the treatment of cardiovascular disease.

MicroRNA-153 inhibits the proliferation and invasion of human laryngeal squamous cell carcinoma by targeting KLF5.

microRNA (miR)-153 has been shown to play a role in several solid malignancies; however, its expression and function in laryngeal squamous cell carcinoma (LSCC) have not been fully explored. In the present study, reverse transcription-quantitative polymerase chain reaction analysis was performed in order to detect the expression levels of miR-153 in mucosal specimens isolated from patients undergoing total laryngectomy. In addition, in vitro experiments were performed to analyze the cellular proliferation and invasion abilities of human epithelial type 2 (HEp-2) cells transfected with miR-153 mimics or miR-153 antisense oligonucleotide (ASO). It was found that miR-153 was downregulated in LSCC tissues. Furthermore, while miR-153 mimics inhibited cell proliferation and invasion, miR-153 ASO promoted HEp-2 cell growth and invasion. At a molecular level, it was predicted by bioinformatics that kruppel-like factor 5 (KLF5) has a miR-153 binding site. Luciferase and protein expression analyses revealed that miR-153 inhibited the protein expression of KLF5. These results suggest that miR-153 may act as a tumor suppressor during LSCC progression via the suppression of KLF5, and could potentially serve as a therapeutic target for LSCC.

MiR-153 as a Tumor Suppressor in Glioblastoma Multiforme is Downregulated by DNA Methylation.

Aberrant DNA hypermethylation contributes to many cancers by silencing structurally normal tumor suppressive genes. MicroRNA-153 (miR-153) exerts a tumor suppressive function in glioblastoma multiforme (GBM) by silencing oncogenic targets. However, the mechanism underlying miR-153 regulation in glioma cells has not been studied. The expression levels of miR-153 were determined by real-time PCR and genomic bisulfite modification technique was used to detect the DNA methylation status in the upstream region of miR-153 in GBM, their matched normal adjacent tissues, and the glioblastoma U87 cell line. Following treatment of cells with 5-aza-2'-deoxycitidine (5-aza-dC), the DNA methylation, gene expression and target proteins levels of miR-153 were determined. This study confirmed that miR-153 is significantly downregulated and hypermethylated in GBM tissues compared to their matched normal adjacent tissues. Increased methylation level of miR-153 was significantly correlated with reduced miR-153 expression in GBM tissue specimens. Demethylation of cells by 5-aza-dC treatment led to reduction of miR-153 methylation level, re-expression of candidate microRNA, and downregulation of its target proteins levels. Our data indicated that miR-153 acts as a tumor suppressor in GBM and is down-regulated by DNA methylation, suggesting that miR-153 may serve as a potential diagnostic or therapeutic target of GBM. (Clin. Lab. 2016;62:573-580. DOI: 10.7754/Clin.Lab.2015.150738)

MicroRNA-153 Regulates NRF2 Expression and is Associated with Breast Carcinogenesis.

Abnormal expression of NRF2 levels in some tumor tissues may enhance drug resistance through various mechanisms. Recent studies have demonstrated a link between dysregulated expression of miRNAs and breast carcinogenesis. Quantitative RT-PCR analysis was used to examine the expression levels of miR-153 in breast cancer cell lines. The biological effects of miR-153 were assessed in CRC cell lines using clonogenic cell survival assay, mammosphere formation assay, cell migration assay, 8-OHdG estimation assay, and flow cytometry analysis. Quantitative RT-PCR and western blot analyses were employed to evaluate the expression of miR-153 targets. In this study, we investigated the role of vitamin C in the regulation of miR-153 (miR-153) and its target gene(s) in cell models of mammary carcinogenesis. In human breast cell lines treated with E2, the level of miR-153 was found to be increased. In contrast, vitamin C treatment was able to decrease the expression of miR-153. Bioinformatic prediction indicates nuclear factor erythroid 2-related factor 2 (NRF2) may be a target for miR-153. In E2-treated breast cancer cell lines, NRF2 protein level was found to be decreased. Overexpression of miR-153 significantly reduced NRF2 and the downstream genes. Furthermore, miR-153 was found to decrease apoptosis and increase colony formation in breast epithelial cells. These data indicate that miR-153 acts as an oncogene in breast carcinogenesis by targeting NRF2.

MiR-153 regulates metastases of gastric cancer through Snail.

MicroRNAs (miRNAs) play critical roles in tumorigenesis and cancer metastases of gastric carcinoma (GC). Recently, miR-153 was reported as a tumor suppressor miRNA silenced in GC, whereas the underlying mechanisms are much lacking. Here, we reported that miR-153 levels were significantly decreased and Snail levels were significantly increased in GC specimens, compared to paired adjacent non-tumor gastric tissue. Moreover, the levels of miR-153 and Snail were inversely correlated. Bioinformatics analyses and luciferase reporter assay showed that miR-153 targeted the 3'-untranslated region (3'-UTR) of Snail messenger RNA (mRNA) to inhibit its translation. Overexpression of miR-153 inhibited Snail-mediated cell invasiveness, while depletion of miR-153 increased Snail-mediated cell invasiveness in both Transwell cell migration assay and scratch wound healing assay. Thus, our data suggest that miR-153 suppression in GC promotes Snail-mediated cancer metastases. Re-establishment of miR-153 levels in GC may suppress cancer invasion.

The anti-fibrotic effects of microRNA-153 by targeting TGFBR-2 in pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial fibrotic lung disease with an undefined etiology and no effective treatments. By binding to cell surface receptors, transforming growth factor-β (TGF-β) plays a pivotal role in lung fibrosis. Therefore, the screening of microRNAs (miRNAs), especially those interrupting the effects of TGF-β, may provide information not only on the pathomechanism, but also on the treatment of this disease. In the present study, we found that miR-153 expression was dysregulated in the lungs of mice with experimental pulmonary fibrosis and TGF-β1 decreased miR-153 expression in pulmonary fibroblasts. Moreover, increased miR-153 levels attenuated, whereas the knock down of miR-153 promoted the pro-fibrogenic activity of TGF-β1, and miR-153 reduced the contractile and migratory activities of fibroblasts. In addition, TGFBR2, a transmembrane serine/threonine kinase receptor for TGF-β, was identified as a direct target of miR-153. Furthermore, by post-transcriptional regulation of the expression of TGFBR2, phosphorylation of SMAD2/3 was also influenced by miR-153. These data suggest that miR-153 disturbs TGF-β1 signal transduction and its effects on fibroblast activation, acting as an anti-fibrotic element in the development of pulmonary fibrosis.