Hsa-miR-134-5p predicts cardiovascular risk in circulating mononuclear cells and improves angiogenic action of senescent endothelial progenitor cells.

This research explores the role of microRNA in senescence of human endothelial progenitor cells (EPCs) induced by replication. Hsa-miR-134-5p was found up-regulated in senescent EPCs where overexpression improved angiogenic activity. Hsa-miR-134-5p, which targeted transforming growth factor ß-activated kinase 1-binding protein 1 (TAB1) gene, down-regulated TAB1 protein, and inhibited phosphorylation of p38 mitogen-activated protein kinase (p38) in hsa-miR-134-5p-overexpressed senescent EPCs. Treatment with siRNA specific to TAB1 (TAB1si) down-regulated TAB1 protein and subsequently inhibited p38 activation in senescent EPCs. Treatment with TAB1si and p38 inhibitor, respectively, showed angiogenic improvement. In parallel, transforming growth factor Beta 1 (TGF-ß1) was down-regulated in hsa-miR-134-5p-overexpressed senescent EPCs and addition of TGF-ß1 suppressed the angiogenic improvement. Analysis of peripheral blood mononuclear cells (PBMCs) disclosed expression levels of hsa-miR-134-5p altered in adult life, reaching a peak before 65 years, and then falling in advanced age. Calculation of the Framingham risk score showed the score inversely correlates with the hsa-miR-134-5p expression level. In summary, hsa-miR-134-5p is involved in the regulation of senescence-related change of angiogenic activity via TAB1-p38 signalling and via TGF-ß1 reduction. Hsa-miR-134-5p has a potential cellular rejuvenation effect in human senescent EPCs. Detection of human PBMC-derived hsa-miR-134-5p predicts cardiovascular risk.

Blood-derived microRNAs are related to cognitive domains in the general population.

INTRODUCTION: Blood-derived microRNAs (miRNAs) are potential candidates for detecting and preventing subclinical cognitive dysfunction. However, replication of previous findings and identification of novel miRNAs associated with cognitive domains, including their relation to brain structure and the pathways they regulate, are still lacking. METHODS: We examined blood-derived miRNAs and miRNA co-expression clusters in relation to cognitive domains, structural magnetic resonance imaging measures, target gene expression, and genetic variants in 2869 participants of a population-based cohort. RESULTS: Five previously identified and 14 novel miRNAs were associated with cognitive domains. Eleven of these were also associated with cortical thickness and two with hippocampal volume. Multi-omics analysis showed that certain identified miRNAs were genetically influenced and regulated genes in pathways like neurogenesis and synapse assembly. DISCUSSION: We identified miRNAs associated with cognitive domains, brain regions, and neuronal processes affected by aging and neurodegeneration, making them promising candidate blood-based biomarkers or therapeutic targets of subclinical cognitive dysfunction. HIGHLIGHTS: We investigated the association of blood-derived microRNAs with cognitive domains. Five previously identified and 14 novel microRNAs were associated with cognition. Eleven cognition-related microRNAs were also associated with cortical thickness. Identified microRNAs were linked to genes associated with neuronal functions. Results provide putative biomarkers or therapeutic targets of cognitive aging.

miR-134-5p inhibits osteoclastogenesis through a novel miR-134-5p/Itgb1/MAPK pathway.

Osteoporosis affects approximately 200 million people and severely affects quality of life, but the exact pathological mechanisms behind this disease remain unclear. Various miRNAs have been shown to play a predominant role in the regulation of osteoclast formation. In this study, we explored the role of miR-134-5p in osteoclastogenesis both in vivo and in vitro. We constructed an ovariectomized (OVX) mouse model and performed microarray analysis using bone tissue from OVX mice and their control counterparts. Quantitative RT-PCR data from bone tissue and bone marrow macrophages (BMMs) confirmed the decreased expression of miR-134-5p in OVX mice observed in microarray analysis. In addition, a decrease in miR-134-5p was also observed during induced osteoclastogenesis of BMMs collected from C57BL/6N mice. Through transfection with miR-134-5p agomirs and antagomirs, we found that miR-134-5p knockdown significantly accelerated osteoclast formation and cell proliferation and inhibited apoptosis. Furthermore, a luciferase reporter assay showed that miR-134-5p directly targets the integrin surface receptor gene Itgb1. Cotransfection with Itgb1 siRNA reversed the effect of the miR-134-5p antagomir in promoting osteoclastogenesis. Moreover, the abundance levels of MAPK pathway proteins phosphorylated-p38 (p-p38) and phosphorylated-ERK (p-ERK) were significantly increased after transfection with the miR-134-5p antagomir but decreased after transfection with the miR-134-5p agomir or Itgb1 siRNA, which indicated a potential relationship between the miR-134-5p/Itgb1 axis and the MAPK pathway. Collectively, these results revealed that miR-134-5p inhibits osteoclast differentiation of BMMs both in vivo and in vitro and that the miR-134-5p/Itgb1/MAPK pathway might be a potential target for osteoporosis therapy.

Spinal microRNA-134-5p targets glutamate receptor ionotropic kainate 3 to modulate opioid induced hyperalgesia in mice.

Background: Fentanyl and its analogs are extensively used for pain relief. However, their paradoxically pronociceptive effects often lead to increased opioids consumption and risk of chronic pain. Compared to other synthetic opioids, remifentanil has been strongly linked to acute opioid hyperalgesia after exposure [remifentanil-induced hyperalgesia (RIH)]. The epigenetic regulation of microRNAs (miRNAs) on targeted mRNAs has emerged as an important pathogenesis in pain. The current research aimed at exploring the significance and contributions of miR-134-5p to the development of RIH. Methods: Both the antinociceptive and pronociceptive effects of two commonly used opioids were assessed, and miRNA expression profiles in the spinal dorsal horn (SDH) of mice acutely exposed to remifentanil and remifentanil equianalgesic dose (RED) sufentanil were screened. Next, the candidate miRNA level, cellular distribution, and function were examined by qPCR, fluorescent in situ hybridization (FISH) and Argonaute-2 immunoprecipitation. Furthermore, bioinformatics analysis, luciferase assays, miRNA overexpression, behavioral tests, golgi staining, electron microscopy, whole-cell patch-clamp recording, and immunoblotting were employed to investigate the potential targets and mechanisms underlying RIH. Results: Remifentanil induced significant pronociceptive effects and a distinct miRNA-profile from sufentanil when compared to saline controls. Among top 30 differentially expressed miRNAs spectrum, spinal miR-134-5p was dramatically downregulated in RIH mice but remained comparative in mice subjected to sufentanil. Moreover, Glutamate Receptor Ionotropic Kainate 3 (Grik3) was a target of miR-134-5p. The overexpression of miR-134-5p attenuated the hyperalgesic phenotype, excessive dendritic spine remodeling, excitatory synaptic structural plasticity, and Kainate receptor-mediated miniature excitatory postsynaptic currents (mEPSCs) in SDH resulting from remifentanil exposure. Besides, intrathecal injection of selective KA-R antagonist was able to reverse the GRIK3 membrane trafficking and relieved RIH. Conclusion: The miR-134-5p contributes to remifentanil-induced pronociceptive features via directly targeting Grik3 to modulate dendritic spine morphology and synaptic plasticity in spinal neurons.

Circ_0002111/miR-134-5p/FSTL1 signal axis regulates tumor progression and glycolytic metabolism in papillary thyroid carcinoma cells.

BACKGROUND: Circular RNAs (circRNAs) have essential roles in the malignant progression of papillary thyroid carcinoma (PTC). Circ_0002111 was reported to facilitate cell proliferation and invasion abilities in PTC. This study was performed to explore the regulatory mechanism of circ_0002111 in PTC progression. METHODS: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used for the level detection of circ_0002111, microRNA-134-5p (miR-134-5p) and Follistatin Like 1 (FSTL1). Cell proliferation was assessed by 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay, EdU assay and colony formation assay. Cell migration ability was determined by transwell assay. Glycolysis was analyzed by extracellular acidification rate (ECAR), oxygen consumption rate (OCR), glucose consumption and lactate production. The protein quantification was performed through western blot. Xenograft tumor assay was used for the functional analysis of circ_0002111 in vivo. The target interaction was confirmed by dual-luciferase reporter assay and RNA pull-down assay. RESULTS: The significant upregulation of circ_0002111 was detected in PTC samples and cells. PTC cell proliferation, migration and glycolytic metabolism were suppressed after circ_0002111 downregulation. PTC tumorigenesis in vivo was also inhibited by circ_0002111 knockdown. In addition, circ_0002111 could target miR-134-5p and si-circ_0002111#1-induced inhibition of PTC progression was relieved by miR-134-5p expression downregulation. Furthermore, FSTL1 was a target gene for miR-134-5p and miR-134-5p served as a tumor repressor in PTC by targeting FSTL1. Moreover, circ_0002111 could increase the FSTL1 level via sponging miR-134-5p. CONCLUSION: All results indicated that circ_0002111 promoted the malignant behaviors of PTC cells partly by regulating the miR-134-5p/FSTL1 molecular network.

CircDLGAP4 induces autophagy and improves endothelial cell dysfunction in atherosclerosis by targeting PTPN4 with miR-134-5p.

OBJECTIVE: Circular RNAs (circRNAs), a new subgroup of non-coding RNAs in the human transcriptome, are crucial in atherosclerosis (AS). Here, a newly identified circRNA circDLGAP4 was demonstrated to be downregulated in oxidized forms of low-density lipoprotein (ox-LDL)-induced HUVECs. METHODS: This research adopted ox-LDL to stimulate human umbilical vein endothelial cells (HUVECs) to mimic AS in vitro. To further validate the protective action of circDLGAP4 in AS, a mouse model of AS was constructed with a high-fat diet. Functional assays evaluated circDLGAP4 role in AS in vitro and in vivo. Moreover, mechanism assays evaluated association of circDLGAP4/miR-134-5p/PTPN4. RESULTS: CircDLGAP4 was induced to promote cell proliferative behavior and autophagy, inhibit apoptotic and inflammatory activities in ox-LDL-treated HUVECs, and attenuated endothelial barrier function. CircDLGAP4 regulated PTPN4 by directly targeting miR-134-5p. Meanwhile, inhibiting miR-134-5p reduced ox-LDL-induced cell dysfunction. Knockout of PTPN4 reversed circDLGAP4 overexpression or miR-134-5p downregulation in vitro. In addition, reducing circDLGAP4 or overexpressing miR-134-5p increased the red atherosclerotic plaque and lesion area of AS mice, reduced autophagy level, and promoted the release of inflammatory cytokines. CONCLUSION: This study extends the role of circRNA in AS by inducing autophagy and improving endothelial dysfunction in AS via the circDLGAP4/miR-134-5p/PTPN4 axis.

Self-assembled miR-134-5p inhibitor nanoparticles ameliorate experimental bronchopulmonary dysplasia (BPD) via suppressing ferroptosis.

Bronchopulmonary dysplasia (BPD) is a chronic lung disease in premature infants with increased levels of reactive oxygen species (ROS) and ferroptosis. Herein, we designed a peptide-based nanoparticle to deliver therapeutic molecules to pulmonary, thereby ameliorating BPD. The BPD-induced damages of lung tissues were detected by H&E and immunohistochemistry staining. Inflammatory cytokines, Fe2+, and ROS levels were quantified by the indicated kits, respectively. The targeting relationship was verified by luciferase reporter assay and pull-down assay. Subsequently, self-assembled miR-134-5p inhibitor nanoparticles with pulmonary epithelial cell-targeting were synthesized. The characteristics were detected by transmission electron microscopy, luminescence imaging, and dynamic light scattering. A significant ferroptosis was observed in the BPD mice. The protein level of GPX4 was decreased significantly compared to the control group. Constantly, miR-134-5p showed positive regulation on ferroptosis by targeting GPX4. The designed nanoparticles were mainly accumulated in the lung region. Besides, it ameliorated experimental bronchopulmonary dysplasia via suppressing ferroptosis, in vivo and in vitro. Our findings provided a miR-134-5p/GPX4 axis in regulating ferroptosis of BPD and prompted the potential of applying the peptide-based nanoparticle to BPD treatment.

Long non-coding RNA SNHG7 upregulates FGF9 to alleviate oxygen and glucose deprivation-induced neuron cell injury in a miR-134-5p-dependent manner.

Long non-coding RNA small nucleolar RNA host gene 7 (SNHG7) was reported to regulate the pathogenesis of ischemic stroke. The study aimed to disclose SNHG7 role in oxygen and glucose deprivation (OGD)-induced Neuro-2a (N2a) cell disorders. An OGD injury cell model was established using N2a cells. The expression of SNHG7, microRNA-134-5p (miR-134-5p) and fibroblast growth factor 9 (FGF9) was determined by quantitative real-time polymerase chain reaction. Protein expression was detected by western blot. Cell viability and Lactate Dehydrogenase (LDH) leakage were determined by cell counting kit-8 and LDH activity detection assays. Oxidative stress was investigated by Superoxide Dismutase and Catalase activity assays as well as Malondialdehyde and Reactive Oxygen Species detection kits. Cell apoptosis and caspase-3 activity were severally demonstrated by flow cytometry and caspase-3 activity assays. The interaction between miR-134-5p and SNHG7 or FGF9 was predicted by online databases, and identified by mechanism assays. OGD treatment decreased SNHG7 and FGF9 expression, but increased miR-134-5p expression. OGD treatment repressed cell viability, promoted LDH leakage and induced oxidative stress and apoptosis in N2a cells, which was rescued by SNHG7 overexpression. SNHG7 acted as a sponge for miR-134-5p, and regulated OGD-triggered cell damage by associating with miR-134-5p. Additionally, miR-134-5p depletion protected N2a cells from OGD-induced injury by targeting FGF9. Ectopic SNHG7 expression protected against OGD-induced neuronal cell injury by inducing FGF9 through sponging miR-134-5p, providing a novel therapeutic target for ischemic stroke.

Exosome miR-134-5p restrains breast cancer progression via regulating PI3K/AKT pathway by targeting ARHGAP1.

AIM: Exosomes has been shown to be involved in the regulation of cancer progression. However, the role of exosome miR-134-5p in breast cancer (BC) progression is unclear. METHODS: Exosomes were extracted from BC cells (MCF-7 and MDA-MB-231) using differential centrifugation and were observed by transmission electron microscope (TEM). The protein levels of exosome markers, apoptosis markers, Rho GTPase activating protein 1 (ARHGAP1, an important oncogene in BC) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) markers were detected by western blot (WB) assay. Quantitative real-time PCR was used to measure the expression levels of miR-134-5p and ARHGAP1. Cell cycle and apoptosis, colony number, viability, migration, and invasion were determined by flow cytometry, colony formation assay, MTT assay, and transwell assay, respectively. The interaction between miR-134-5p and ARHGAP1 was confirmed using a dual-luciferase reporter assay. Xenograft models were constructed to verify the role of exosome miR-134-5p in BC tumor growth in vivo. RESULTS: MiR-134-5p was lowly expressed in BC cells and in the exosomes of BC cells. Overexpressed exosome miR-134-5p suppressed the proliferation, migration, invasion, and promoted the apoptosis of BC cells. ARHGAP1 was a target of miR-134-5p, and its silencing could inhibit BC progression. In addition, ARHGAP1 overexpression could reverse the negative regulation of miR-134-5p on BC progression. MiR-134-5p could target ARHGAP1 to inhibit the activity of PI3K/AKT pathway. Exosome miR-134-5p overexpression could suppress BC tumor growth via targeting ARHGAP1 in vivo. CONCLUSION: Exosome miR-134-5p restrained BC progression through regulating ARHGAP1/PI3K/AKT signaling pathway, suggesting that miR-134-5p might be a therapeutic target for BC.

The microRNA miR-134-5p induces calcium deposition by inhibiting histone deacetylase 5 in vascular smooth muscle cells.

Calcium deposition in vascular smooth muscle cells (VSMCs) is a form of ectopic ossification in blood vessels. It can result in rigidity of the vasculature and an increase in cardiac events. Here, we report that the microRNA miR-134-5p potentiates inorganic phosphate (Pi)-induced calcium deposition in VSMCs by inhibiting histone deacetylase 5 (HDAC5). Using miRNA microarray analysis of Pi-treated rat VSMCs, we first selected miR-134-5p for further evaluation. Quantitative RT-PCR confirmed that miR-134-5p was increased in Pi-treated A10 cells, a rat VSMC line. Transfection of miR-134-5p mimic potentiated the Pi-induced increase in calcium contents. miR-134-5p increased the amounts of bone runt-related transcription factor 2 (RUNX2) protein and bone morphogenic protein 2 (BMP2) mRNA in the presence of Pi but decreased the expression of osteoprotegerin (OPG). Bioinformatic analysis showed that the HDAC5 3'untranslated region (3'UTR) was one of the targets of miR-134-5p. The luciferase construct containing the 3'UTR of HDAC5 was down-regulated by miR-134-5p mimic in a dose-dependent manner in VSMCs. Overexpression of HDAC5 mitigated the calcium deposition induced by miR-134-5p. Our results suggest that a Pi-induced increase of miR-134-5p may cause vascular calcification through repression of HDAC5.

Circular RNA circDLGAP4 exerts neuroprotective effects via modulating miR-134-5p/CREB pathway in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disease which is characterized by the substantia nigra dopaminergic neurons denatured. Circular RNA (circRNA) DLGAP4 (circDLGAP4) was found to have neuroprotective effect. In this study, we aimed to investigate whether circDLGAP4 participates in the progression of PD. Here, our results showed that circDLGAP4 expression was decreased in MPTP-induced PD mouse model and MPP+-induced PD cell models. In vitro study revealed that circDLGAP4 could promote viability, reduce apoptosis, decrease mitochondrial damage, enhance autophagy and thereby attenuated the neurotoxic effects of MPP+ in SH-SY5Y and MN9D cells. Further research suggested that circDLGAP4 exerted its functions via regulating miR-134-5p. Moreover, we demonstrated that CREB was a target of miR-134-5p and CREB expression could be regulated by circDLGAP4/miR-134-5p axis. CircDLGAP4/miR-134-5p could also modulate the activation of CREB signaling and thereby influence the expression of CREB target genes including BDNF, Bcl-2 and PGC-1α in SH-SY5Y and MN9D cells. In all, our study identifies that circDLGAP4 exerts neuroprotective effects via modulating miR-134-5p/CREB pathway both in human and mouse.

MiR-134-5p targeting XIAP modulates oxidative stress and apoptosis in cardiomyocytes under hypoxia/reperfusion-induced injury.

MicroRNA-134-5p (MiR-134-5p) has been proposed as a promising novel biomarker for the diagnosis of acute myocardial infarction (AMI). However, the biological role of miR-134-5p in ischemic cardiomyocytes has been little disclosed yet. Expression of miR-134-5p and X-linked inhibitor of apoptosis protein (XIAP) was detected using RT-qPCR and western blot. Oxidative stress and cell apoptosis were determined by enzyme-linked immunosorbent assays, 3-(4, 5-dimethylthiazole-2-y1)-2, 5-biphenyl tetrazolium bromide assay, flow cytometry, western blot, and terminal-deoxynucleoitidyl transferase-mediated nick end labeling (TUNEL). The interaction between miR-134-5p and XIAP was confirmed by luciferase reporter assay. Expression of miR-134-5p was upregulated in serum of AMI patients and hypoxia/reoxygenation (H/R)-induced cardiomyocytes (AC16 and HCM). MiR-134-5p downregulation could inhibit H/R-mediated release of lactic dehydrogenase enzyme (LDH) and malondialdehyde (MDA), and promote superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) levels. Meanwhile, cell viability was increased, while the apoptosis rate and TUNEL positive cells were inhibited by miR-134-5p downregulation in H/R-treated AC16 and HCM cells. Mechanically, XIAP was downregulated and targeted by miR-134-5p in H/R-induced cardiomyocytes in vitro. Overexpression of XIAP inhibited oxidative stress and cell apoptosis in H/R-treated AC16 and HCM cells, which was similar to miR-134-5p knockdown. Moreover, downregulation of XIAP could partially reverse the effect of miR-134-5p knockdown in H/R-induced cardiomyocytes. Knockdown of miR-134-5p protected cardiomyocytes from H/R-induced oxidative stress and apoptosis in vitro through targeting XIAP.

SMAD6, positively regulated by the DNM3OS-miR-134-5p axis, confers promoting effects to cell proliferation, migration and EMT process in retinoblastoma.

BACKGROUND: Retinoblastoma (RB) is acknowledged to be the commonest intraocular malignancy in infants and children and the outcome of RB patients is unfavorable due to limited early diagnosis and effective therapy. SMAD family member 6 (SMAD6) has been reported in the initiation and progression of human cancers by acting as a biological participant. However, the role of SMAD6 in RB has not been illustrated yet. METHODS: The expression of SMAD6 mRNA, miR-134-5p and DNM3OS was measured by RT-qPCR. SMAD6 protein levels were measured by western blot. The effects of SMAD6 depletion on RB cells were analyzed using CCK-8 and transwell assays. The key proteins related to epithelial-mesenchymal transition (EMT) was determined by western blot. The localization of DNM3OS was detected by nuclear/cytoplasmic assay. In addition, the direct interaction between miR-134-5p and SMAD6 or DNM3OS was confirmed with the application of dual-luciferase reporter assay. RESULTS: SMAD6 was upregulated in RB tissue samples and cell lines, and silencing SMAD6 suppressed cell proliferation, migration and EMT in RB. Mechanically, SMAD6 was positively regulated by lncRNA DNM3OS through competitively interacting with miR-134-5p. DNM3OS contributed to RB progression by SMAD6-mediated manner. CONCLUSIONS: This research unmasked a novel DNM3OS/miR-134-5p/SMAD6 pathway in RB, which might make contribution to treatment of RB.

Long non-coding RNA LINC00858 aggravates the oncogenic phenotypes of ovarian cancer cells through miR-134-5p/RAD18 signaling.

PURPOSE: Ovarian cancer is a common gynecological cancer. Herein, we focused on the function and probable mechanisms of LINC00858 in ovarian cancer. METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was employed for detecting the expression of LINC00858, miR-134-5p and RAD18 E3 ubiquitin protein ligase (RAD18). Cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT) and apoptosis were detected by cell counting kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), transwell, terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) and western bolt experiments, as appropriate. Interplays between LINC00858, miR-134-5p and RAD18 were detected by RNA immunoprecipitation (RIP), RNA pull down and luciferase reporter assays. RESULTS: LINC00858 were up-regulated in ovarian cancer tissues and cells, and its expression was elevated in advanced samples compared to early ones. Knocking down LINC00858 inhibited cell proliferation, motility and EMT, but accelerated cell apoptosis in ovarian cancer. Moreover, could be sponged by LINC00858 sponged miR-134-5p to enhance RAD18 expression in ovarian cancer. Also, silenced RAD18 could also restrain oncogenic behaviors of ovarian cancer cells. Rescue experiments showed that overexpressing RAD18 reversed the effects caused by knocking down LINC00858 on cellular processes. CONCLUSION: LINC00858 sequestered miR-134-5p to elevate RAD18 expression, resulting in aggravated development of ovarian cancer. This might provide promising targets for treating patients with ovarian cancer.

miR-134-5p inhibition reduces infarct-induced cardiomyocyte apoptosis via Creb1 upregulation.

BACKGROUND: Following the recent discovery that microRNA-134-5p (miR-134-5p) is elevated in the early stages of acute myocardial infarction (AMI), we examined the specific role of miR-134-5p in cardiomyocytes during AMI. METHODS: To study miR-134-5p's role in the context of AMI, we used a combination of in vitro experiments in H2O2-treated or hypoxic cardiomyocyte cell cultures as well as in vivo experiments in a murine model of AMI. RESULTS: H2O2- and hypoxia-induced cardiomyocyte injury upregulated miR-134-5p expression. miR-134-5p overexpression increased cardiomyocyte apoptosis, whereas miR-134-5p inhibition reduced cardiomyocyte apoptosis. We discovered that the transcription factor cAMP-responsive element binding protein 1 (Creb1) is a functional target of miR-134-5p responsible for regulating cardiomyocyte apoptosis. In vivo AMI resulted in the upregulation and downregulation of miR-134-5p and Creb1 in the infarct area, respectively. Circulating miR-134-5p levels were also increased at days 1 and 2 post-AMI. Modulation of myocardial miR-124-5p expression by intramyocardial injection of antagomiR-134-5p or agomiR-134-5p significantly affected cardiomyocyte apoptosis, infarct size, and cardiac function in vivo. CONCLUSIONS: miR-134-5p/Creb1 axis dysregulation plays a role in hypoxia- or oxidative stress-induced cardiomyocyte apoptosis as well as AMI. Circulating miR-134-5p may show promise as a biomarker for AMI or post-AMI cardiac dysfunction. Manipulating the miR-134-5p/Creb1 axis through either inhibition of miR-134-5p or overexpression of Creb1 may show promise as a novel therapeutic strategy to attenuate cardiac dysfunction following AMI.

MiR-134-5p attenuates neuropathic pain progression through targeting Twist1.

Neuropathic pain is a kind of chronic pain because of dysfunctions of somatosensory nerve system. Recently, many studies have demonstrated that microRNAs (miRs) play crucial roles in neuropathic pain development. This study was designed to investigate the effects of miR-134-5p on the process of neuropathic pain progression in a rat model established by chronic sciatic nerve injury (CCI). First, we observed that miR-134-5p was significantly decreased in CCI rat models. Overexpression of miR-134-5p strongly alleviated neuropathic pain behaviors including mechanical and thermal hyperalgesia. Meanwhile, inflammatory cytokine expression, such as IL-6, IL-1ß and TNF-α in CCI rats were greatly repressed by upregulation of miR-134-5p. Twist1 has been widely regarded as a poor prognosis biomarker in diverse diseases. Here, by using bioinformatic analysis, 3'-untranslated region (UTR) of Twist1 was predicted to be a downstream target of miR-134-5p in our study. Here, we found that overexpression of miR-134-5p was able to suppress Twist1 dramatically. Furthermore, it was exhibited that Twist1 was increased in CCI rats time-dependently and Twist1 was inhibited in vivo. Subsequently, downregulation of Twist1 in CCI rats could depress neuropathic pain progression via inhibiting neuroinflammation. In conclusion, our current study indicated that miR-134-5p may inhibit neuropathic pain development through targeting Twist1. Our findings suggested that miR-134-5p might provide a novel therapeutic target for neuropathic pain.

Long non-coding RNA PCAT7 regulates ELF2 signaling through inhibition of miR-134-5p in nasopharyngeal carcinoma.

While some long noncoding RNAs (lncRNAs) might promote nasopharyngeal carcinoma (NPC) initiation and progression, the involved molecular mechanisms remain largely unclear. Here, we discovered the novel LncRNA, prostate cancer associated transcript 7 (PCAT7), which was overexpressed and associated with worse prognosis in NPC. Decreased PCAT7 expression was found to significantly suppress tumor cell proliferation in vitro, and inhibited tumor growth and reduced the expression of proliferation antigen Ki-67 in vivo. Rescue assay was performed to further confirm that PCAT7 contributed to the progression of NPC through regulating miR-134-5p/ELF2 signal pathway. These results indicated that PCAT7 might contribute to the tumor progression in NPC by functioning as a ceRNA to sponge miR-134-5p.

Curcumin targets miR-134-5p to suppress the progression of colorectal cancer through regulating the CDCA3/CDK1 pathway.

It has been reported the anti-tumor action of curcumin on colorectal cancer. In this study, we aimed to explore the potential mechanisms underlying curcumin in the development of colorectal cancer. CCK-8, EdU, flow cytometry, and transwell invasion assays were conducted to investigate the function role of curcumin in cell proliferation, apoptosis, and invasion. The level of miR-134-5p and CDCA3 was determined using RT-qPCR analysis. Western blot was applied for detecting the levels of c-myc, MMP9, CDCA3, and CDK1. Dual-luciferase reporter assay was used to evaluate the relationship between miR-134-5p and CDCA3, and IP assay was performed to examine the interaction between CDCA3 and CDK1. Additionally, SW620 cells were injected into the mice to form the xenograft tumor model. Curcumin treatment repressed cell growth and invasion, and induced cell apoptosis in HCT-116 and SW620 cells. Curcumin elevated miR-134-5p expression and restrained CDCA3 expression in HCT-116 and SW620 cells. MiR-134-5p inhibitor or CDCA3 overexpression could restore the effects of curcumin on cell growth, apoptosis, and invasion in HCT-116 and SW620 cells. MiR-134-5p targeted CDCA3, and CDCA3 could rescue the repressive effects of miR-134-5p on the progression of colorectal cancer. Moreover, CDCA3 interacted with CDK1, and CDK1 overexpression blocked the suppressive effects of CDCA3 downregulation on the development of colorectal cancer. In addition, curcumin treatment repressed tumor growth in colorectal cancer via increasing miR-134-5p and downregulating CDCA3 and CDK1 expression in vivo. Our findings provided the evidence that curcumin upregulated miR-134-5p to inhibit the progression of colorectal cancer by regulating CDCA3/CDK1 pathway.

circ_0029463 promotes osteoclast differentiation by mediating miR-134-5p/Rab27a axis.

OBJECTIVE: Osteoporosis is the imbalance in bone homeostasis between osteoblasts and osteoclasts. In this study, we investigated the effects of the circ_0029463/miR-134-5p/Rab27a axis on RANKL-induced osteoclast differentiation. METHODS: RT-qPCR and western blotting were used to detect the expression of circ_0029463, miR-134-5p, and Rab27a in tissues from patients with osteoporosis and in RANKL-induced osteoclasts. Osteoclast differentiation was verified by TRAP staining. Osteoclast biomarkers, including NFATc1, TRAP, and CTSK, were measured. The target and regulatory relationships between circ_0029463, miR-134-5p, and the Rab27a axis were verified using RIP, dual-luciferase reporter gene, and RNA pull-down assays. RESULTS: Elevated expression of circ_0029463 and Rab27a and decreased miR-134-5p expression were observed in the tissues of patients with osteoporosis, and a similar expression pattern was observed in RANKL-induced osteoclasts. Suppression of circ_0029463 expression or miR-134-5p overexpression curbed RANKL-induced osteoclast differentiation, whereas such an effect was abolished by Rab27 overexpression. circ_0029463 sponges miR-134-5p to induce Rab27a expression. CONCLUSION: circ_0029463 sponges miR-134-5p to abolish its suppressive effect of miR-134-5p on Rab27a expression, thereby promoting osteoclast differentiation.

has-miR-134-5p inhibits the proliferation and migration of glioma cells by regulating the BDNF/ERK signaling pathway.

Our research investigated the effects of hsa-miR-134-5p on glioma progression, focusing on its interaction with the BDNF/ERK signaling pathway. U251 and U87 cell lines were analyzed post-transfection with hsa-miR-134-5p mimics and inhibitors, confirming the miRNA's binding to BDNF using dual luciferase assays. Q-PCR was employed to measure expression changes, revealing that hsa-miR-134-5p markedly inhibited glioma cell proliferation, migration, and invasion, as evidenced by CCK8, monoclonal formation, and Transwell assays. Scratch tests and Western blotting demonstrated hsa-miR-134-5p's modulation of the BDNF/ERK pathway and associated decrease in MMP2/9 protein levels. Flow cytometry suggested that hsa-miR-134-5p might also block the G0/S phase transition. In vivo studies using nude mice corroborated the tumor-suppressing effects of hsa-miR-134-5p, which were negated by elevated BDNF levels. Comparative protein analysis across groups confirmed the pathway's significance in tumorigenesis. Our findings identify hsa-miR-134-5p as a key molecule impeding glioma cell growth by curtailing the BDNF/ERK pathway, with the reversal by BDNF upregulation pointing to the potential of therapeutically exploiting the hsa-miR-134-5p/BDNF axis in glioma care.