The role of miRNA134 in pathogenesis and treatment of intractable epilepsy: a review article.

MicroRNA-134 (miRNA134) has emerged as a critical regulator in the pathogenesis of epilepsy, particularly in intractable cases resistant to conventional therapies. This review explores the multifaceted roles of miRNA134 in epileptogenesis, focusing on its influence on dendritic spine morphology and synaptic plasticity. Through its interactions with proteins such as LIM kinase 1 (LIMK1), Pumilio 2 (PUM2), and Tubby-like protein 1 (TULP1), miRNA134 modulates various molecular pathways implicated in epilepsy development. Preclinical studies have shown pro-mising results in targeting miRNA134 for mitigating seizure activity, highlighting its potential as a therapeutic target. Furthermore, miRNA134 holds promise as a biomarker for epilepsy diagnosis and prognosis, offering opportunities for personalized treatment approaches. However, further research is warranted to elucidate the precise mechanisms underlying miRNA134's effects and to translate these findings into clinical applications.

Changes in miR-134-3p expression and zDHHC3-AMPARs axis in association with aluminum neurotoxicity.

Aluminum (Al) is a neurotoxic substance associated with cognitive dysfunction and neurodegenerative diseases, such as Alzheimer's disease, but the mechanisms for aluminum neurotoxicity remain to be identified. In this work, we try to investigate a novel potential biomarker of cognitive dysfunction following aluminum exposure and the mechanism involved. Recently, miR-134-3p was reported as a novel regulator of cognitive function. To address this, we investigate the expression level of miR-134-3p in plasma from 280 aluminum factory workers and analyzed the correlation between miRNA-134-3p, blood Al concentration, and Montreal Cognitive Assessment Scale (MoCA scale) score. The results implied that occupational aluminum exposure elevated miR-134-3p expression in the plasma of workers accompanied by cognitive impairment. Our experiment studies using both animal models and PC12 cells validated the upregulation of miR-134-3p caused by aluminum. In addition, we identified that palmitoylation enzyme zDHHC3 was the target of miR-134-3p, and the decreasing AMPAR receptor (AMPAR) trafficking was related to the learning and memory impairment induced by aluminum. More importantly, using transfection and interference approaches in PC12 cells, inhibition of miR-134-3p resulted in a recovery of zDHHC3-AMPARs axis to a certain extent in response to aluminum. In summary, miR-134-3p was found to be involved in aluminum neurotoxicity by targeting zDHHC3-AMPARs axis and could serve as a potential biomarker or helpful target.

Long non­coding RNA PCAT1 sponges miR­134­3p to regulate PITX2 expression in breast cancer.

Breast cancer (BC) is the most prevalent cancer among women. Long non­coding (lnc)RNAs and microRNAs (miRs) both regulate the expression of key genes in tumorigenesis. The present study aimed to explore the molecular mechanism of the prostate cancer­associated transcript 1 (PCAT1)/miR­134­3p/pituitary homeobox 2 (PITX2) in BC. Reverse transcription­quantitative PCR was performed to examine the expression of miR­134­3p. Cell proliferation, viability, cell cycle, apoptosis and migration were analyzed using Cell Counting Kit­8, colony formation, flow cytometry, wound healing and Transwell assays. Protein expression levels were determined by western blotting. The present study demonstrated that PCAT1 was significantly highly expressed in BC cells. Knockdown of PCAT1 significantly inhibited cell proliferation, migration and invasion, but promoted apoptosis in human BC cell lines. The results of the dual­luciferase assay showed that PCAT1 targeted miR­134­3p, and PITX2 was a potential target of miR­134­3p. Western blotting results demonstrated that PCAT1 knockdown significantly reduced the protein expression levels of anti­apoptotic protein Bcl­2, and significantly upregulated the protein expression levels of proapoptotic proteins, Bax, cleaved caspase­3 and cleaved caspase­9. Furthermore, the effect of a miR­134­3p inhibitor on BC progression was rescued by the knockdown of PITX2 in cells transfected with short hairpin RNA­lncRNA PCAT1. To conclude, the results of the present study indicated that the PCAT1/miR­134­3p/PITX2 axis could be a promising therapeutic target in BC treatment.

Establishment and evaluation of a compound fear behavior model of Tourette's syndrome in rats.

BACKGROUND: Tourette syndrome (TS) is a common childhood disorder characterized by unwanted movements or vocal sounds called tics. It is often accompanied by other psychobehavioral disorders, including fearful behavior. The establishment and evaluation of rat models of TS and comorbid fear can provide an experimental basis for the treatment of TS and its comorbid fear disorder. METHODS: Sixteen rats were randomly divided into a model group (n=8) and control group (n=8). In the model group, rats were injected intraperitoneally with iminodipropionitrile (IDPN) for 1 week to establish the TS model, which was followed by acoustic and electrical stimulation for 3 weeks to establish the rat models of TS and comorbid fear. The control group received intraperitoneal injection of saline for 1 week, and no further intervention was given in the last 3 weeks. The behavioral changes of the rats were observed and analyzed by the open field test (OFT). Protein kinase A (PKA), cyclic adenosine monophosphate (cAMP), and dopamine (DA) were measured by enzyme-linked immunosorbent assay (ELISA), and tyrosine hydroxylase (TH) and microRNA-134 (miRNA-134) in the brain tissue were detected by using polymerase chain reaction (PCR). RESULTS: One rat in the model group died on the 24th day. Compared with the control group, the model group had significantly higher scores of locomotor activity, stereotyped behavior, and motor behavior, along with prolonged freezing time and significantly lower expression of miRNA-134. The differences in the expressions of PKA, cAMP, DA, and TH in brain tissue were not statistically significant. CONCLUSIONS: The rat models of TS and comorbid fear have similar changes in behaviors and miRNA-134 level to those in clinical settings and therefore can be used as a reliable animal model to study the mechanism of action of TS and comorbid fear.

Transcription factor ELK1 accelerates aerobic glycolysis to enhance osteosarcoma chemoresistance through miR-134/PTBP1 signaling cascade.

Osteosarcoma is a malignancy that primarily affects children and young adults. The poor survival is largely attributed to acquisition of chemoresistance. Thus, the current study aimed to elucidate the role of ELK1/miR-134/PTBP1 signaling cascade in osteosarcoma chemoresistance. Doxorubicin (DXR)-resistant human osteosarcoma cells were initially self-established by continuous exposure of MG-63, U2OS and HOS cells to increasing DXR doses. Osteosarcoma chemoresistance in vitro was evaluated using CCK-8 assays and EdU staining. Aerobic glycolysis was evaluated by lactic acid production, glucose consumption, ATP levels, and Western blot analysis of GLUT3, HK2 and PDK1 proteins. The nude mice were injected with 5.0 mg/kg DXR following the subcutaneous transplantation of osteosarcomas. PTBP1 was upregulated in tumor tissues derived from non-responders to DXR treatment and correlated with patient poor survival. PTBP1 enhanced chemoresistance in cultured osteosarcoma cells in vitro and in vivo by increasing aerobic glycolysis. Additionally, miR-134 inhibited translation of PTBP1. ELK1 bound to miR-134 promoter and inhibited its expression. Overexpressed ELK1 enhanced chemoresistance and increased aerobic glycolysis by downregulating miR-134 and upregulating PTBP1 in DXR-resistant cells. Altogether, the key findings of the present study highlight ELK1/miR-134/PTBP1 signaling cascade as a novel molecular mechanism underlying the acquisition of osteosarcoma chemoresistance.

Predictive Value of Circulating microRNA-134 Levels for Early Diagnosis of Acute Pulmonary Embolism: Meta-analysis.

Acute pulmonary embolism (APE) is a common sudden venous thromboembolism with high rates of morbidity and mortality. Several studies have concluded that microRNA-134 could be a potential biomarker for APE. However, the sensitivity of these studies varies widely. This study aimed to evaluate the diagnostic value of circulating microRNA-134 levels for APE. Four databases were searched to retrieve articles focusing on microRNA-134 detection in APE diagnosis. The Quality Assessment of Diagnostic Accuracy Studies-2 was used to evaluate the quality of the included literature. This meta-analysis included seven studies and 383 subjects. The microRNA-134 levels in APE patients were higher than those in controls (SMD = 2.84, z = 3.69, p < 0.001). The pooled sensitivity, specificity, and diagnostic odds ratio were 0.86 (0.72-0.94), 0.75 (0.66-0.82), and 19 (7-51), respectively. The positive and negative likelihood ratios were 3.4 (2.4-4.8) and 0.18 (0.08-0.40), respectively. The area under the summary receiver operating characteristic curve was 0.81 (0.77-0.84). Circulating microRNA-134 may be a new biomarker for the diagnosis of APE, but more tests and studies are needed to further explore and prove this. Trial registration number: PROSPERO registration #CRD42020184072.

Silencing of Long Non-coding RNA TTN-AS1 Inhibits Hepatocellular Carcinoma Progression by the MicroRNA-134/ITGB1 Axis.

BACKGROUND: Hepatocellular carcinoma (HCC) causes considerable mortality worldwide. Long non-coding RNA (lncRNA) TTN-AS1 has been recently identified as an oncogene in several cancers, but its role in HCC and the molecules remain largely unknown. AIMS: The study aims to probe the function of lncRNA TTN-AS1 in HCC progression and the molecules involved. METHODS: Differentially expressed lncRNAs between HCC and the adjacent normal tissues were analyzed using a microarray. TTN-AS1 expression in HCC and normal tissues and cells was determined. Targeting relationships between TTN-AS1 and miR-134 and between miR-134 and ITGB1 were validated. Artificial up-regulation or down-regulation of TTN-AS1, miR-134 and ITGB1 was introduced in HCC cells to probe their effects on the biological behaviors of HCC cells. Xenograft tumors were induced in nude mice for in vivo experiments. RESULTS: TTN-AS1 and ITGB1 were highly expressed, while miR-134 was poorly expressed in HCC tissues. TTN-AS1 enforced ITGB1 expression through sequestering miR-134. Silencing of TTN-AS1 or over-expression of miR-134 inhibited proliferation, invasion, migration, and resistance to death of Huh7 cells. Following miR-134 silencing, further down-regulation of ITGB1 suppressed the malignant behaviors of HUH7 cells. The similar results were reproduced in vivo. CONCLUSION: The current study provided evidence that TTN-AS1 might promote HCC progression through sponging miR-134 and the following ITGB1 up-regulation. TTN-AS1 may serve as a potential target for HCC treatment.

Exogenous delivery of microRNA-134 (miR-134) using α-tocopherol-based PEGylated liposome for effective treatment in skin squamous cell carcinoma.

MicroRNAs (miRNAs) are involved in the pathogenesis of several cancers including skin squamous cell carcinoma (sSCC), and miR-134 is reported to possess tumor inhibition properties. The present study is an attempt to study the mechanistic role and antitumor property of miR-134 in sSCC. For this purpose, α-tocopherol PEG 1000 succinate (TPGS)-based PEGylated liposome was formulated and encapsulated with miR-134 (TP-miR-LP). CCK-8 assay results showed that miR-134 exhibited a concentration-dependent decrease in the cell viability of A-431 cells. Importantly, TPGS-based TP-miR-LP showed significantly (p < 0.05) lower cell viability compared with that of miR-134-loaded PEGylated liposome (miR-LP). Western blot analysis clearly indicates the specific targeting ability of miR-134 (TP-miR-LP) towards the Forkhead Box M1 (FOXM1) in the cancer cells. The apoptosis rate of the cells was significantly increased in TP-miR-LP (~ 38%) than that of miR-LP (~ 15%), respectively with significant inhibition of cell migration. Importantly, tumors treated with TP-miR-LP grew significantly slower compared with that of any other formulation group in the xenograft animal model. Present results clearly demonstrate the tumor suppressive effect of miR-134 through the downregulation of FOXM1 which subsequently blocks the downstream signaling pathways. These findings suggest the translational potential of miR-134 towards designing formulation strategies for sSCC treatment. Graphical abstract.

MicroRNA-134-3p inhibits ovarian cancer progression by targeting flap structure-specific endonuclease 1 in vitro.

Ovarian cancer (OC) is one of the most lethal gynecological malignancies in the world. The aim of the present study was to examine the role of microRNA (miR)-134-3p in OC. Reverse transcription-quantitative PCR was used to measure the expression levels of miR-134-3p. Cell Counting Kit-8, TUNEL, flow cytometric and colony formation assays were performed to examine the effects of miR-134-3p on OC cell proliferation. Moreover, wound healing and Transwell assays were performed to examine the effects on migration and invasion. In addition, western blot analyses were used to assess protein expression. Finally, the target genes of miR-134-3p were analyzed by bioinformatics analysis and dual-luciferase reporter assay. The results revealed that miR-134-3p expression was low in OC cells compared with in normal ovarian cells. The overexpression of miR-134-3p decreased cell viability, facilitated cell apoptosis, inhibited cell proliferation and arrested the cell cycle in SKOV-3 and OVCAR-3 cells. Furthermore, transfection using a miR-134-3p mimic inhibited the migration and invasion of SKOV-3 and OVCAR-3 cells, and decreased the protein expression levels of cyclooxygenase-2, matrix metalloproteinase (MMP)2 and MMP9. Bioinformatics analysis indicated that one of the potential target genes of miR-134-3p was flap structure-specific endonuclease 1 (FEN1), which was confirmed by dual-luciferase reporter assay. Moreover, overexpression of miR-134-3p decreased the expression levels of FEN1 in SKOV-3 and OVCAR-3 cells. Additionally, overexpression of FEN1 reversed the effects of the miR-134-3p mimic on the proliferation, migration and invasion of SKOV-3 and OVCAR-3 cells. Overall, the findings of the present study demonstrated that miR-134-3p may inhibit OC cell proliferation, migration and invasion by directly targeting FEN1.

SDF-1α/MicroRNA-134 Axis Regulates Nonfunctioning Pituitary Neuroendocrine Tumor Growth via Targeting VEGFA.

Background: Nonfunctioning pituitary neuroendocrine tumor (NF-PitNET) is difficult to resect. Except for surgery, there is no effective treatment for NF-PitNET. MicroRNA-134 (miR-134) has been reported to inhibit proliferation and invasion ability of tumor cells. Herein, the mechanism underlying the effect of miR-134 on alleviating NF-PitNET tumor cells growth is explored. Methods: Mouse pituitary αT3-1 cells were transfected with miR-134 mimics and inhibitor, followed by treatment with stromal cell-derived factor-1α (SDF-1α) in vitro. MiR-134 expression level: we used quantitative real-time PCR (qRT-PCR) to detect the expression of miR-134. Cell behavior level: cell viability and invasion ability were assessed using a cell counting kit-8 (CCK8) assay and Transwell invasion assay respectively. Cytomolecular level: tumor cell proliferation was evaluated by Ki-67 staining; propidium iodide (PI) staining analyzed the effect of miR-134 on cell cycle arrest; western blot analysis and immunofluorescence staining evaluated tumor migration and invasive ability. Additionally, we collected 27 NF-PitNET tumor specimens and related clinical data. The specimens were subjected to qRT-PCR to obtain the relative miR-134 expression level of each specimen; linear regression analysis was used to analyze the miR-134 expression level in tumor specimens and the age of the NF-PitNET population, gender, tumor invasion, prognosis, and other indicators. Results: In vitro experiment, miR-134 was observed to significantly inhibit αT3-1 cells proliferation characterized by inhibited cell viability and expressions of vascular endothelial growth factor A (VEGFA) and cell cycle transition from G1 to S phase (P < 0.01). VEGFA was verified as a target of miR-134. Additionally, miR-134-induced inhibition of αT3-1 cell proliferation and invasion was attenuated by SDF-1α and VEGFA overexpression (P < 0.01). In primary NF-PitNET tumor analysis, miR-134 expression level was negatively correlated with tumor invasion (P = 0.003). Conclusion: The regulation of the SDF-1α/miR-134/VEGFA axis represents a novel mechanism in the pathogenesis of NF-PitNETs and may serve as a potential therapeutic target for the treatment of NF-PitNETs.

C/EBPα-mediated transcriptional activation of miR-134-5p entails KPNA3 inhibition and modulates focal hypoxic-ischemic brain damage in neonatal rats.

Hypoxic-ischemic brain damage (HIBD) is a frequent cause of mortality and neurological handicaps in infants and children worldwide. To understand better the pathogenesis and management of HIBD, we established a HIBD model by common carotid artery ligation followed by systemic hypoxia in neonatal rats, and in other studies induced neuronal death in rat pheochromocytoma (PC12) cells by 12 h of oxygen-glucose deprivation (OGD). The level of KPNA3 declined in rats following experimental HIBD and in PC12 cells following OGD. KPNA3 overexpression protected neonatal rats against HIBD and PC12 cells against OGD-induced cell death. KPNA3 demonstrated to be the target of miR-134-5p could be activated by the transcriptional factor CCAAT/enhancer binding protein alpha (C/EBPα). The expression of miR-134-5p and C/EBPα was elevated in rats following experimental HIBD and in PC12 cells following OGD. In the parallel experiments, C/EBPα knockdown and miR-134 inhibition protected against HIBD pathology in neonatal rats and against OGD-induced neuronal death in PC12 cells. These findings reveal that the C/EBPα/miR-134-5p/KPNA3 axis mediates hypoxic-ischemic brain damage and neuronal death, thus presenting a potential therapeutic target for the treatment of human newborns at risk for HIBD.

Protective effect of microRNA-134-3p on multiple sclerosis through inhibiting PRSS57 and promotion of CD34+ cell proliferation in rats.

MicroRNAs (miRs) have been extensively studied for their involvement in multiple sclerosis (MS). We investigated the involvement of miR-134-3p on MS. The MS rat model was established, and positive expression of interleukin-17 (IL-17) was detected using the immunohistochemical method while the expression of miR-134-3p and serine protease 57 (PRSS57) was determined by means of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Second, the miR-134-3p overexpression or short hairpin RNA against PRSS57 was introduced into the CD34+ cells to investigate the levels of proliferation and apoptosis-related genes by RT-qPCR and Western blot analysis. In addition, analysis of the targeting relations of miR-134-3p and PRSS57 was conducted using online software and dual-luciferase reporter gene assay. Furthermore, neuronal functions, inflammatory response, proliferation, and apoptosis of CD34+ cells were assayed by flow cytometry, enzyme-linked immunosorbent assay, and methyl thiazolyl tetrazolium. IL-17 and PRSS57 expression increased while miR-134-3p expression decreased in the spinal cord from MS rats. miR-134-3p could target PRSS57. miR-134-3p overexpression or PRSS57 silencing enhanced mitochondrial activity of neurons, mitochondrial membrane potential content, CD34+ cell proliferation, while decreasing Cyt C content, inflammatory response, and cell apoptosis. Collectively, overexpression of miR-134-3p promotes CD34+ cell proliferation via inhibition of PRSS57 in MS, which may serve as a promising target for MS intervention.

MicroRNA-134 inhibits tumor stem cell migration and invasion in oral squamous cell carcinomas via downregulation of PI3K-Akt signaling pathway by inhibiting LAMC2 expression.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common malignant neoplasm of the mouth. Some studies have found that multiple microRNAs (miRs) participate in OSCC physiological and pathological processes. METHODS: We explored the mechanism of action of miR-134 in OSCC involving the PI3K-Akt signaling pathway. Different bioinformatics methods were used to analyze the potential genes and their related miRs in OSCC. Tumor stem cells were separated from OSCCs through magnetic cell sorting. Regulatory pattern between miR-134 and LAMC2 in OSCC was evaluated by ectopic expression, knockdown and reporter assay experiments. The expression of miR-134, LAMC2, genes in PI3K-Akt signaling pathway, and apoptosis-related genes was detected. Cell proliferation was assessed by MTT assay, cell invasion by scratch test, cell migration by Transwell assay, cell cycle and apoptosis by flow cytometry, and cell growth and migration by xenograft tumor in nude mice. LAMC2 was predicted as the crucial factor related to OSCC using different chip data, and miR-134 was predicted to specifically bind LAMC2 in all five databases. RESULTS: Overexpressed miR-134 or silenced LAMC2 was observed to inhibit cell proliferation, migration, invasion of OSCC cells, growth of subcutaneous xenograft in nude mice, as well as promote OSCC cell apoptosis. LAMC2, a target gene of miR-134, decreased following miR-134 promotion, while the PI3K-Akt signaling pathway was inactivated following LAMC2 knockdown. Furthermore, we also observed that the effect of overexpressed miR-134 was enhanced when LAMC2 was knocked down. CONCLUSIONS: Taken together, these findings suggest that miR-134-mediated direct downregulation of LAMC2 inhibits migration and invasion of tumor stem cells in OSCC by suppressing the PI3K-Akt signaling pathway.

MicroRNA-134 prevents the progression of esophageal squamous cell carcinoma via the PLXNA1-mediated MAPK signalling pathway.

BACKGROUND: MicroRNAs (miRNAs) are involved in oncogenesis of esophageal squamous cell carcinoma (ESCC). miR-134 is reported to have a tumour-suppressive role but its role in ESCC is not known. The present study was designed to examine whether miR-134 inhibits ESCC development and further explored relevant underlying mechanisms. METHODS: Differentially expressed genes related to ESCC were identified from microarray gene expression profiles. Immunohistochemical staining and RT-qRCR assays identified elevated PLXNA1 expression levels and low miR-134. The relationship between miR-134 and PLXNA1 was predicted and further verified by a dual-luciferase reporter assay. The expression levels of miR-134 and PLXNA1 in ESCC cells were modified by miR-134 mimic/inhibitor and siRNA against PLXNA1, respectively. Thereafter, the expression of MAPK signalling pathway-related proteins, as well as the viability, migration, invasion, cell cycle and cell apoptosis of ESCC cells was investigated. FINDINGS: The results showed that miR-134 could block the MAPK signalling pathway by downregulating PLXNA1. When miR-134 was overexpressed or PLXNA1 was silenced, cell apoptosis was enhanced, the cell cycle was retarded, and the cell proliferation, migration and invasion were suppressed. In vivo experiments confirmed that miR-134 overexpression or PLXNA1 silencing restrained tumour growth and lymph node metastasis. INTERPRETATION: These findings demonstrate that cancer cell proliferation, migration, invasion, and tumour metastasis of ESCC can be suppressed by overexpression of miR-134 through downregulating PLXNA1, which subsequently blocks the MAPK signalling pathway. These results provide new potential targets and strategies for the treatment of ESCC.

Silencing of long non-coding RNA NCK1-AS1 inhibits cell proliferation and migration via inhibition of microRNA-134 in cervical cancer.

Long non-coding RNA NCK1-antisense 1 (AS1) has recently been demonstrated to promote cell proliferation and induce cell cycle progression through the crosstalk NCK1-AS1/microRNA (miR)-6857/cyclin dependent kinase 1 pathway in cervical cancer. However, the regulatory mechanism of NCK1-AS1 in cervical cancer growth and metastasis remains largely unclear. In the present study, it was identified that NCK1-AS1 was significantly upregulated in cervical cancer tissues compared with the levels in adjacent non-tumour tissues. High expression levels of NCK1-AS1 were associated with tumour progression and poor prognosis in patients with cervical cancer. Silencing of NCK1-AS1 expression significantly decreased the levels of proliferation and migration of cervical cancer cells, and decreased the protein expression levels of matrix metalloproteinase (MMP)-2 and MMP-9. The results of the luciferase reporter gene assay indicated that there was an miR-134 binding site within the NCK1-AS1 gene in cervical cancer cells. miR-134 was significantly downregulated in cervical cancer tissues compared with the miR-134 levels in adjacent non-tumour tissues, and the expression level of miR-134 was inversely correlated with the NCK1-AS1 expression levels in cervical cancer tissues. Knockdown of miR-134 attenuated the inhibitory effects of NCK1-AS1 downregulation on the proliferation and migration of cervical cancer cells. Therefore, the data from the present study suggested that NCK1-AS1 serves a promotive role in cervical cancer cell proliferation and migration by functioning as a molecular sponge for miR-134. NCK1-AS1 may become a novel therapeutic target for cervical cancer.

Silencing MicroRNA-134 Alleviates Hippocampal Damage and Occurrence of Spontaneous Seizures After Intraventricular Kainic Acid-Induced Status Epilepticus in Rats.

Epilepsy is a disorder of abnormal brain activity typified by spontaneous and recurrent seizures. MicroRNAs (miRNAs) are short non-coding RNAs, critical for the post-transcriptional regulation of gene expression. MiRNA dysregulation has previously been implicated in the induction of epilepsy. In this study, we examined the effect of silencing miR-134 against status epilepticus (SE). Our results showed that level of miR-134 was significantly up-regulated in rat brain after Kainic acid (KA)-induced SE. TUNEL staining showed that silencing miR-134 alleviated seizure-induced neuronal apoptosis in the CA3 subfield of the hippocampus. Western blot showed that a miR-134 antagonist suppressed lesion-induced endoplasmic reticulum (ER) stress and apoptosis related expression of CHOP, Bim and Cytochrome C, while facilitated the expression of CREB at 24 h post KA-induced lesion in the hippocampus. Consistently, silencing miR-134 significantly diminished loss of CA3 pyramidal neurons using Nissl staining as well as reducing aberrant mossy fiber sprouting (MFS) in a rat epileptic model. In addition, the results of EEG and behavior analyses showed seizures were alleviated by miR-134 antagonist in our experimental models. These results suggest that silencing miR-134 modulates the epileptic phenotype by upregulating its target gene, CREB. This in turn attenuates oxidative and ER stress, inhibits apoptosis, and decreases MFS long term. This indicates that silencing miR-134 might be a promising intervention for the treatment of epilepsy.

Suppression of long noncoding RNA NCK1-AS1 increases chemosensitivity to cisplatin in cervical cancer.

Cervical cancer remains a serious health problem till now, with nearly 500,000 women cases diagnosed each year around the world. Long noncoding RNA (lncRNA) is a novel class of RNA transcripts (>200 nucleotides in length) participating in gene transcription, cell proliferation, differentiation, and drug resistance. This study aimed to explore the regulatory relationship among lncRNA NCK1-AS1, miR-134-5p, and MutS protein homolog 2 (MSH2), so that the resistance against cisplatin in cervical cancer treatment could be better understood. Comprehensive lncRNA profiling analysis was performed to screen lncRNAs differentially expressed in cervical cancer. The expression patterns of miR-134-5p, NCK1-AS1, and MSH2 were evaluated in cancerous tissues and adjacent normal tissues obtained from 75 cervical cancer patients. Subsequently, anti-NCK1-AS1 small interfering RNA, miR-134-5p mimics, and miR-134-5p inhibitors were transfected into cervical cancer cells, and the effects of these transcripts on cisplatin resistance and cell apoptosis were investigated. The regulatory relationship among NCK1-AS1, miR-134-5p, and MSH2 was identified using a dual-luciferase reporter gene assay, and the results were further validated by RNA pull-down and RNA immunoprecipitation assays. Based on the microarray data of GSE63514 and GSE27678, NCK1-AS1 was upregulated in cervical cancer. Increased expression of NCK1-AS1, MSH2, and decreased expression of miR-134-5p were observed in cervical cancer tissues. In addition, NCK1-AS1 competitively bound to miR-134-5p to regulate MSH2. Therefore, si-NCK1-AS1 and miR-134-5p mimic both reduced MSH2 activity and increased cisplatin-induced apoptosis in cervical cancer cells. Taken together, NCK1-AS1 may become a novel target in improving the chemotherapeutic response and survival of cervical cancer patients.

Spared CA1 pyramidal neuron function and hippocampal performance following antisense knockdown of microRNA-134.

OBJECTIVE: Inhibition of microRNA-134 by an oligonucleotide antagomir (ant-134) has been shown to produce powerful antiseizure effects in multiple models of epilepsy. However, to successfully translate the treatment to the clinic, it is important to assess what potential adverse effects it may have on naive brain tissue. METHODS: To investigate this, adult male Sprague-Dawley rats were treated with either ant-134 or a scrambled control sequence. Animals were later assessed for spatial navigation, before ex vivo slices were taken to assess the effects of microRNA-134 knockdown on well-defined measures of intrinsic and synaptic properties. RESULTS: Hippocampal field potential recordings determined that silencing of microRNA-134 by ant-134 injection was associated with a reduction in epileptiform activity following application of 9 mmol/L K+ . Nevertheless, rats performed normally in the novel object location test. Action potential waveforms and miniature excitatory synaptic currents recorded in CA1 pyramidal neurons were unaffected by ant-134. SIGNIFICANCE: These results demonstrate that ant-134 confers a seizure-protective effect without obvious interference with hippocampal neuronal properties or network function. These findings support further development of this novel approach to epilepsy treatment.

Effects of microRNA-134 on proliferation and apoptosis of non-small cell lung cancer by regulating P53 protein / 国际肿瘤学杂志

Objective To investigate the effects of microRNA-134 (miR-134) on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) and its potential molecular mechanism.Methods Quantitative real-time fluorescent polymerase chain reaction (qRT-PCR) was used to detect the differences of miR-134 expression between 10 cases of lung cancer tissues and normal lung tissues,and between normal human lung epithelial cell line BEAS-2B and lung adenocarcinoma cell line A549.miR-NC and miR-134 mimic were transfected into A549 cells.The effect of miR-134 on proliferation of A549 cells was detected by methyl thiazolyl tetrazolium (MTT) and colony form experiment.Flow cytometry was used to determine the effect of miR-134 on A549 cells apoptosis.The effect of miR-134 on the expression of P53 protein was detected by Western blotting.Results The relative expressions of miR-134 in NSCLC tumor tissues and adjacent tissues were 0.429 ± 0.126 and 0.971 ±0.183 respectively,and the difference was statistically significant (t =7.742,P ＜0.001).The relative expressions of miR-134 in BEAS-2B cells and A549 cells were 1.013 ± 0.095 and 0.371 ± 0.068 respectively,and the difference was statistically significant (t =17.377,P ＜ 0.001).The absorbance (A) values of A549 cells transfected with miR-mimic were 0.451 ±0.051 and 0.518 ±0.074 on the third and forth day respectively,and those of A549 cells transfected with miR-NC were 0.683 ± 0.041 and 0.815 ± 0.065 respectively.The proliferation ability of miR-mimic group was significantly lower than that of miR-NC group (t =12.965,P ＜ 0.001;t =9.535,P ＜ 0.001).The colony forming rates of A549 cells transfected with miR-NC and miR-134 mimic were 91.2％ ± 8.3％ and 38.6％ ±4.5％ respectively,and the colony forming rate of A549 cells in miR-134 mimic group was significantly decreased (t =17.617,P ＜0.001).The apoptosis rates of miR-134 mimic group and miR-NC group were 93.5％ ± 3.7％ and 85.4％ ± 2.0％ respectively,and the difference was significant difference (t =6.119,P ＜ 0.001).The relative expressions of P53 protein in miR-134 mimic group and miR-NC group were 1.816 ±0.173 and 0.992 ± 0.096 respectively,and the difference was statistically significant (t =19.308,P ＜ 0.001).Conclusion miR-134 can be an effective target for the treatment of NSCLC by increasing the protein expression of P53,inhibiting the viability and proliferation of tumor cells,and promoting the apoptosis of tumor cells.

MicroRNA-134 plasma levels before and after treatment with valproic acid for epilepsy patients.

BACKGROUND: Temporal lobe epilepsy is the second most common neurological disorders characterized by recurrent spontaneous seizures. MicroRNAs play a vital role in regulating synaptic plasticity, brain development and post-transcriptional expression of proteins. In both animal models of epilepsy and human patients, miR-134, a brain-specific microRNA has recently been identified as a potential regulator of epileptogenesis. METHODS: microRNA identified as targets for the actions of valproic acid (VPA) are known to have important effects in brain function. In this study, 59 new-onset epilepsy patients and 20 controls matched by sex and age were enrolled. Patients with a score < 3 were allocated into the mild group, 3-5 into the moderate group and >5 into the severe group. The plasma miRNA-134 level was quantitatively measured using real-time PCR. RESULTS: Plasma miRNA-134 level in new-onset epilepsy patients was significantly up-regulated when compared with that in healthy controls, and then considerably down-regulated after oral intake of valproic acid medication. The up-regulated plasma miRNA-134 levels may be directly associated with the pathophysiology and severity of epilepsy. CONCLUSION: Plasma miRNA-134 in epilepsy may be considered as a potential peripheral biomarker that responds to the incidence of epilepsy and associates with use of anti-epilepsy drugs.