MiRNA-210 is involved in cigarette smoke extract-induced apoptosis of MLE-12 via the Shh signaling pathway.

INTRODUCTION: The aim of the study is the regulatory effect of MicroRNA-210 (MiR-210) on cigarette smoke extract (CSE)-induced mouse lung epithelial type II cells (MLE-12) apoptosis and determine whether the MiR-210 is involved in cigarette smoke extract-induced apoptosis of MLE-12 via Shh signaling pathway. METHODS: Expression of MiR-210 in CSE-induced MLE-12 was assessed by qRT-PCR. The emphysema mouse model and MiR-210 knockdown mice were each established by inhaling cigarette smoke or intratracheal lentiviral vector instillation. The Sonic hedgehog (Shh), Ptch1, Gli1, B-cell lymphoma-2 (Bcl-2), and Caspase 3 protein expressions were detected by Western blotting. mRNA expressions of MiR-210, Shh, Ptch1, and Gli1 were measured using quantitative real-time polymerase chain reaction (qRT-PCR). Apoptotic ratios in mice and CSE-induced HPVEC were assessed using TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays and flow cytometry. RESULTS: Our results showed that MiR-210 mRNA levels were significantly down-regulated in the CSE-induced MLE 12. MLE 12 apoptosis with down-regulated Shh, Ptch1, Gli1, and Bcl-2 expression, increased Caspase 3 expression in the emphysema mouse model and CSE-induced MLE 12. Knockdown MiR-210 can facilitate cell apoptosis and emphysema via the Shh signaling pathway in mice. In vitro, MiR-210 can attenuate the apoptosis of CSE-exposed MLE 12. Moreover, MiR-210 regulated the Shh pathway and promoted its expression. CONCLUSIONS: MiRNA-210 is involved in cigarette smoke extract-induced apoptosis of MLE-12 via the Shh signaling pathway. The present study reveals that MiRNA-210 may be a key regulator of cellular apoptosis and could be explored as a potential therapeutic target in the future.

lncRNA Biomarkers of Glioblastoma Multiforme.

Long noncoding RNAs (lncRNAs) are RNA molecules of 200 nucleotides or more in length that are not translated into proteins. Their expression is tissue-specific, with the vast majority involved in the regulation of cellular processes and functions. Many human diseases, including cancer, have been shown to be associated with deregulated lncRNAs, rendering them potential therapeutic targets and biomarkers for differential diagnosis. The expression of lncRNAs in the nervous system varies in different cell types, implicated in mechanisms of neurons and glia, with effects on the development and functioning of the brain. Reports have also shown a link between changes in lncRNA molecules and the etiopathogenesis of brain neoplasia, including glioblastoma multiforme (GBM). GBM is an aggressive variant of brain cancer with an unfavourable prognosis and a median survival of 14-16 months. It is considered a brain-specific disease with the highly invasive malignant cells spreading throughout the neural tissue, impeding the complete resection, and leading to post-surgery recurrences, which are the prime cause of mortality. The early diagnosis of GBM could improve the treatment and extend survival, with the lncRNA profiling of biological fluids promising the detection of neoplastic changes at their initial stages and more effective therapeutic interventions. This review presents a systematic overview of GBM-associated deregulation of lncRNAs with a focus on lncRNA fingerprints in patients' blood.

Adipose tissue macrophage-derived microRNA-210-3p disrupts systemic insulin sensitivity by silencing GLUT4 in obesity.

Management of chronic obesity-associated metabolic disorders is a key challenge for biomedical researchers. During chronic obesity, visceral adipose tissue (VAT) undergoes substantial transformation characterized by a unique lipid-rich hypoxic AT microenvironment which plays a crucial role in VAT dysfunction, leading to insulin resistance (IR) and type 2 diabetes. Here, we demonstrate that obese AT microenvironment triggers the release of miR-210-3p microRNA-loaded extracellular vesicles from adipose tissue macrophages, which disseminate miR-210-3p to neighboring adipocytes, skeletal muscle cells, and hepatocytes through paracrine and endocrine actions, thereby influencing insulin sensitivity. Moreover, EVs collected from Dicer-silenced miR-210-3p-overexpressed bone marrow-derived macrophages induce glucose intolerance and IR in lean mice. Mechanistically, miR-210-3p interacts with the 3'-UTR of GLUT4 mRNA and silences its expression, compromising cellular glucose uptake and insulin sensitivity. Therapeutic inhibition of miR-210-3p in VAT notably rescues high-fat diet-fed mice from obesity-induced systemic glucose intolerance. Thus, targeting adipose tissue macrophage-specific miR-210-3p during obesity could be a promising strategy for managing IR and type 2 diabetes.

LncRNA MIR210HG promotes phenotype switching of pulmonary arterial smooth muscle cells through autophagy-dependent ferroptosis pathway.

Hypoxic pulmonary hypertension (HPH) is a pathophysiological syndrome in which pulmonary vascular pressure increases under hypoxic stimulation and there is an urgent need to develop emerging therapies for the treatment of HPH. LncRNA MIR210HG is a long non-coding RNA closely related to hypoxia and has been widely reported in a variety of tumor diseases. But its mechanism in hypoxic pulmonary hypertension is not clear. In this study, we identified for the first time the potential effect of MIR210HG on disease progression in HPH. Furthermore, we investigated the underlying mechanism through which elevated levels of MIR210HG promotes the transition from a contractile phenotype to a synthetic phenotype in PASMCs under hypoxia via activation of autophagy-dependent ferroptosis pathway. While overexpression of HIF-2α in PASMCs under hypoxia significantly reversed the phenotypic changes induced by MIR210HG knockdown. We further investigated the potential positive regulatory relationship between STAT3 and the transcription of MIR210HG in PASMCs under hypoxic conditions. In addition, we established both in vivo and in vitro models of HPH to validate the differential expression of specific markers associated with hypoxia. Our findings suggest a potential mechanism of LncRNA MIR210HG in the progression of HPH and offer potential targets for disease intervention and treatment.

Peritumor Mucosa in Advanced Laryngeal Carcinoma Exhibits an Aberrant Proangiogenic Signature Distinctive from the Expression Pattern in Adjacent Tumor Tissue.

The field cancerization theory is an important paradigm in head and neck carcinoma as its oncological repercussions affect treatment outcomes in diverse ways. The aim of this study is to assess the possible interconnection between peritumor mucosa and the process of tumor neoangiogenesis. Sixty patients with advanced laryngeal carcinoma were enrolled in this study. The majority of patients express a canonical HIF-upregulated proangiogenic signature with almost complete predominancy of HIF-1α overexpression and normal expression levels of the HIF-2α isoform. Remarkably, more than 60% of the whole cohort also exhibited an HIF-upregulated proangiogenic signature in the peritumoral benign mucosa. Additionally, the latter subgroup had a distinctly shifted phenotype towards HIF-2α upregulation compared to the one in tumor tissue, i.e., a tendency towards an HIF switch is observed in contrast to the dominated by HIF-1α tumor phenotype. ETS-1 displays stable and identical significant overexpression in both the proangiogenic phenotypes present in tumor and peritumoral mucosa. In the current study, we report for the first time the existence of an abnormal proangiogenic expression profile present in the peritumoral mucosa in advanced laryngeal carcinoma when compared to paired distant laryngeal mucosa. Moreover, we describe a specific phenotype of this proangiogenic signature that is significantly different from the one present in tumor tissue as we delineate both phenotypes, quantitively and qualitatively. This finding is cancer heterogeneity, per se, which extends beyond the "classical" borders of the malignancy, and it is proof of a strong interconnection between field cancerization and one of the classical hallmarks of cancer-the process of tumor neoangiogenesis.

miR-210-5p Promotes Pulmonary Hypertension by Blocking ATP2A2.

AIM: Aberrant expression of ATPase sarcoplasmic/endoplasmic retic Ca2+ transporting 2 (ATP2A2) has attracted attention for its pathophysiologic role in pulmonary hypertension (PH). Several miRNAs, including miR-210-5p, have also been reported to be pathogenic factors in PH, but their exact mechanisms remain unknown. This study aimed to elucidate the potential mechanisms of miR-210-5p and ATP2A2 in MCT-induced PH. METHODS: Eighteen Sprague-Dawley rats were randomly divided into two groups-monoclonal (MCT) group and control group-and then administered MCT (60 mg/kg) and saline, respectively. mPAP, PVR, RVHI, WT%, and WA% were significantly increased in PH rats after 3 weeks, confirming that the modeling of PH rats was successful. Subsequently, we determined the expression of ATP2A2 and miR-210-5p in lung tissues using WB and qRT-PCR methods. We established an in vitro model using BMP4 and TGF-ß1 treatment of pulmonary artery smooth muscle cells (PASMCs) and examined the expression of ATP2A2 and miR-210-5p using the same method. To further elucidate the regulatory relationship between ATP2A2 and miR-210-5p, we altered the expression level of miR-210-5p and detected the corresponding changes in ATP2A2 levels. In addition, we demonstrated the relationship by dual luciferase experiments. Finally, the effect of silencing ATP2A2 could be confirmed by the level of cell membrane Ca2+ in PAMSCs. RESULTS: Up-regulation of miR-210-5p and down-regulation of ATP2A2 were observed in the MCT group compared with the control group, which was confirmed in the in vitro model. In addition, elevated miR-210-5p expression decreased the level of ATP2A2 while increasing the proliferation of PASMCs, and the results of the dual luciferase assay further confirmed that ATP2A2 is a downstream target of miR-210-5p. Additionally, silencing ATP2A2 resulted in increased cytoplasmic Ca2+ levels in PAMSCs. CONCLUSION: In MCT-induced PH, miR-210-5p promotes pulmonary vascular remodeling by inhibiting ATP2A2.

Correlation analysis of serum miR-145 and miR-210 with carotid artery stenosis and their predictive value for cerebral ischemic events.

OBJECTIVE: To analyze the significance of serum miR-145 and miR-210 expression levels in the diagnosis of carotid artery stenosis. METHODS: During the same period, 55 healthy individuals who received physical examination in the same hospital were recruited as controls and assigned to a non-stenosis group. Among the included patients, there were 45 cases of mild stenosis, 14 cases of moderate stenosis, and 6 cases of severe stenosis after carotid color Doppler ultrasonography. The expression levels of miR-145 and miR-210 in serum were measured using real-time fluorescence quantitative polymerase chain reaction (qPCR) technology. RESULTS: The expression levels of serum miR-145 and miR-210 in carotid artery stenosis group were significantly lower than those in non-stenosis group (p < 0.001). Multivariate Logistic regression analysis showed that smoking history, diabetes, hypertension and total cholesterol were positively correlated with the occurrence of carotid artery stenosis (p < 0.05). The expression levels of miR-145 and miR-210 were significantly negatively correlated with carotid artery stenosis (p < 0.001). In addition, patients with carotid artery stenosis and low expression levels of miR-145 and miR-210 had a greater risk of cerebral ischemia (p < 0.05). Cox regression analysis showed that the low expression of miR-145 and miR-210 were independent predictors of cerebral ischemic events. ROC analysis confirmed that miR-145 and miR-210 had good diagnostic efficacy in cerebral ischemia (p < 0.001). CONCLUSION: The decreased expression of miR-145 and miR-210 in serum is closely related to the diagnostic significance of carotid artery stenosis, and may be used to predict the occurrence of cerebral ischemic events.

Exosomes Derived from Astragaloside IV-pretreated Endothelial Progenitor Cells (AS-IV-Exos) Alleviated Endothelial Oxidative Stress and Dysfunction Via the miR-210/ Nox2/ROS Pathway.

BACKGROUND: Chronic hyperglycemia in diabetes induces oxidative stress, leading to damage to the vascular system. In this study, we aimed to evaluate the effects and mechanisms of AS-IV-Exos in alleviating endothelial oxidative stress and dysfunction caused by high glucose (HG). METHODS: Histopathological changes were observed using HE staining, and CD31 expression was assessed through immunohistochemistry (IHC). Cell proliferation was evaluated through CCK8 and EDU assays. The levels of ROS, SOD, and GSH-Px in the skin tissues of each group were measured using ELISA. Cell adhesion, migration, and tube formation abilities were assessed using adhesion, Transwell, and tube formation experiments. ROS levels in HUVEC cells were measured using flow cytometry. The levels of miR-210 and Nox2 were determined through quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of Nox2, SOD, GSH-Px, CD63, and CD81 was confirmed using WB. RESULTS: The level of miR-210 was reduced in diabetes-induced skin damage, while the levels of Nox2 and ROS increased. Treatment with AS-IV increased the level of miR-210 in EPC-Exos. Compared to Exos, AS-IV-Exos significantly reduced the proliferation rate, adhesion number, migration speed, and tube-forming ability of HGdamaged HUVEC cells. AS-IV-Exos also significantly decreased the levels of SOD and GSH-Px in HG-treated HUVEC cells and reduced the levels of Nox2 and GSH-Px. However, ROS levels and Nox2 could reverse this effect. CONCLUSION: AS-IV-Exos effectively alleviated endothelial oxidative stress and dysfunction induced by HG through the miR-210/Nox2/ROS pathway.

Enzyme-free sensitive SERS biosensor for the detection of thalassemia-associated microRNA-210 using a cascade dual-signal amplification strategy.

BACKGROUND: ß-thalassemia is a blood disorder caused by autosomal mutations. Gene modulation therapy to activate the γ-globin gene to induce fetal hemoglobin (HbF) synthesis has become a new option for the treatment of ß-thalassemia. MicroRNA-210 (miR-210) contributes to studying the mechanism regulating γ-globin gene expression and is a potential biomarker for rapid ß-thalassemia screening. Traditional miRNA detection methods perform well but necessitate complex and time-consuming miRNA sample processing. Therefore, the development of a sensitive, accurate, and simple miRNA level monitoring method is essential. RESULTS: We have developed a non-enzymatic surface-enhanced Raman scattering (SERS) biosensor utilizing a signal cascade amplification of catalytic hairpin assembly reaction (CHA) and proximity hybridization-induced hybridization chain reaction (HCR). Au@Ag NPs were used as the SERS substrate, and methylene blue (MB)- modified DNA hairpins were used as the SERS tags. The SERS assay involved two stages: implementing the CHA-HCR cascade signal amplification strategy and conducting SERS measurements on the resulting product. The HCR was started by the products of target-triggered CHA, which formed lengthy nicked double-stranded DNA (dsDNA) on the Au@Ag NPs surface to which numerous SERS tags were attached, leading to a significant increase in the SERS signal intensity. High specificity and sensitivity for miR-210 detection was achieved by monitoring MB SERS intensity changes. The suggested SERS biosensor has a low detection limit of 5.13 fM and is capable of detecting miR-210 at concentration between 10 fM and 1.0 nM. SIGNIFICANCE: The biosensor can detect miR-210 levels in the erythrocytes of ß-thalassemia patients, enabling rapid screening for ß-thalassemia and suggesting a novel approach for investigating the regulation mechanism of miR-210 on γ-globin gene expression. In the meantime, this innovative technique has the potential to detect additional miRNAs and to become an important tool for the early diagnosis of diseases and for biomedical research.

CD204-positive M2-like tumor-associated macrophages increase migration of gastric cancer cells by upregulating miR-210 to reduce NTN4 expression.

BACKGROUND: Tumor-associated macrophages (TAMs) are the predominant immune cells in the tumor microenvironment and portend poor prognosis. However, the molecular mechanisms underlying the tumor promotion of TAMs have not been fully elucidated. METHODS: Coculture of gastric cancer cells with U937 cells was performed to investigate the impact of TAMs on cancer cell behavior. MicroRNA (miRNA) microarray and bioinformatics were applied to identify the involved miRNAs and the functional target genes. The regulation of the miRNA on its target gene was studied using anti-miRNA and miRNA mimic. RESULTS: Coculture with CD204+ M2-like TAMs increased proliferation, migration, and epithelial-mesenchymal transition of gastric cancer cells. MiR-210 was the most upregulated miRNA in cancer cells identified by miRNA microarray after coculture. In gastric cancer tissues, miR-210 expression was positively correlated with CD204+ M2-like TAM infiltration. Inactivation of miR-210 by antimir attenuated CD204+ M2-like TAMs-induced cancer cell migration. Using pharmacological inhibitors and neutralizing antibodies, CD204+ M2-like TAMs-secreted TNFα was found to upregulate miR-210 through NF-κB/HIF-1α signaling. Bioinformatics analysis showed netrin-4 (NTN4) as a potential target of miR-210 to suppress gastric cancer cell migration. We also found an inverse expression between miR-210 and NTN4 in cancer cells after coculture or in tumor xenografts. Anti-miR-210 increased NTN4 expression, while miR-210 mimics downregulated NTN4 in cancer cells. Reporter luciferase assays showed that MiR-210 mimics suppressed NTN4 3' untranslated region-driven luciferase activity in cancer cells, but this effect was blocked after mutating miR-210 binding site. CONCLUSIONS: CD204+ M2-like TAMs can utilize the TNF-α/NF-κB/HIF-1α/miR-210/NTN4 pathway to facilitate gastric cancer progression.

Pan-cancer analyses identify MIR210HG overexpression, epigenetic regulation and oncogenic role in human tumors and its interaction with the tumor microenvironment.

BACKGROUND: Molecular entities showing dysregulation in multiple cancers may hold great biomarker or therapeutic potential. There is accumulating evidence that highlights the dysregulation of a long non-coding RNA, MIR210HG, in various cancers and its oncogenic role. However, a comprehensive analysis of MIR210HG expression pattern, molecular mechanisms, diagnostic or prognostic significance or evaluation of its interaction with tumor microenvironment across various cancers remains unstudied. METHODS: A systematic pan-cancer analysis was done using multiple public databases and bioinformatic tools to study the molecular role and clinical significance of MIR210HG. We have analyzed expression patterns, genome alteration, transcriptional and epigenetic regulation, correlation with patient survival, immune infiltrates, co-expressed genes, interacting proteins, and pathways associated with MIR210HG. RESULTS: The Pan cancer expression analysis of MIR210HG through various tumor datasets demonstrated that MIR210HG is significantly upregulated in most cancers and increased with the tumor stage in a subset of them. Furthermore, prognostic analysis revealed high MIR210HG expression is associated with poor overall and disease-free survival in specific cancer types. Genetic alteration analysis showed minimal alterations in the MIR210HG locus, indicating that overexpression in cancers is not due to gene amplification. The exploration of SNPs on MIR210HG suggested possible structural changes that may affect its interactions with the miRNAs. The correlation of MIR210HG with promoter methylation was found to be significantly negative in nature in majority of cancers depicting the possible epigenetic regulation of expression of MIR210HG. Additionally, MIR210HG showed negative correlations with immune cells and thus may have strong impact on the tumor microenvironment. Functional analysis indicates its association with hypoxia, angiogenesis, metastasis, and DNA damage repair processes. MIR210HG was found to interact with several proteins and potentially regulate chromatin modifications and transcriptional regulation. CONCLUSIONS: A first pan-can cancer analysis of MIR210HG highlights its transcriptional and epigenetic deregulation and oncogenic role in the majority of cancers, its correlation with tumor microenvironment factors such as hypoxia and immune infiltration, and its potential as a prognostic biomarker and therapeutic target in several cancers.

Use of Therapeutic RNAs to Accelerate Wound Healing in Diabetic Rabbit Wounds.

Introduction: Diabetes mellitus (DM) affects over 422 million people globally. Patients with DM are subject to a myriad of complications, of which diabetic foot ulcers (DFUs) are the most common with ∼25% chance of developing these wounds throughout their lifetime. Innovation: Currently there are no therapeutic RNAs approved for use in DFUs. Use of dressings containing novel layer-by-layer (LbL)-formulated therapeutic RNAs that inhibit PHD2 and miR-210 can significantly improve diabetic wound healing. These dressings provide sustained release of therapeutic RNAs to the wounds locally without systemic side effects. Clinical Problem Addressed: Diabetic foot wounds are difficult to heal and often result in significant patient morbidity and mortality. Materials and Methods: We used the diabetic neuroischemic rabbit model of impaired wound healing. Diabetes was induced in the rabbits with alloxan, and neuroischemia was induced by ligating the central neurovascular bundle of each ear. Four 6-mm full-thickness wounds were created on each ear. A LbL technique was used to conformally coat the wound dressings with chemically modified RNAs, including an antisense oligonucleotide (antimiR) targeting microRNA-210 (miR-210), an short synthetic hairpin RNA (sshRNA) targeting PHD2, or both. Results: Wound healing was improved by the antimiR-210 but not the PHD2-sshRNA. Specific knockdown of miR-210 in tissue as measured by RT-qPCR was ∼8 Ct greater than nonspecific controls, and this apparent level of knockdown (>99%) suggests that delivery to the tissue is highly efficient at the administered dose. Discussion: Healing of ischemic/neuropathic wounds in diabetic rabbits was accelerated upon inhibition of miR-210 by LbL delivery to the wound bed. miR-210 inhibition was achieved using a chemically modified antisense RNA.

Identification and analysis of genes associated with the severity and prognosis of sepsis.

BACKGROUND: With rapid progression, severe illness and high fatality rate, sepsis has become an acute and critical condition that seriously threatens human life and health. OBJECTIVE: To detect miR-210 and miR-494 expression in patients with sepsis and their relationship with severity and prognosis. METHODS: A total of 165 sepsis patients participated, including 105 patients with septic non-shock and 60 patients with septic shock. 53 sepsis patients died in 28 days, and 112 patients survived. The clinical information of all sepsis patients was retrospectively searched and reviewed. Based on the status of 28-day survival, they were categorized into survival group and death group. The expression levels in each group were compared on the first, third and seventh day. The ROC curve was applied to know the expression level of plasma miR-210 and miR-494 to predict the death. RESULTS: The two miRNAs expression of the septic shock group were significantly higher than that in sepsis non-shock group on the first, third and seventh day (all were P< 0.05). The ROC curve found that the AUC combined to predict the death on the third day was the largest, which was 0.925 (95%CI: 0.864-0.983). The sensitivity and specificity were 94.6% and 86.3%, respectively. CONCLUSION: The increased expression levels of plasma miR-210 and miR-494 are closely relevant to the severity and prognosis of sepsis patients. Combining the two items on the third day can predict the death of sepsis patients.

The dual role of MiR-210 in the aetiology of cancer: A focus on hypoxia-inducible factor signalling.

Tumorigenesis exemplifies the complex process of neoplasm origination, which is characterised by somatic genetic alterations and abnormal cellular growth. This multidimensional phenomenon transforms previously dormant cells into malignant equivalents, resulting in uncontrollable proliferation and clonal expansion. Various elements, including random mutations, harmful environmental substances, and genetic predispositions, influence tumorigenesis's aetiology. MicroRNAs (miRNAs) are now recognised as crucial determinants of gene expression and key players in several biological methods, including oncogenesis. A well-known hypoxia-inducible miRNA is MiR-210, which is of particular interest because of its complicated role in the aetiology of cancer and a variation of physiological and pathological situations. MiR-210 significantly impacts cancer by controlling the hypoxia-inducible factor (HIF) signalling pathway. By supporting angiogenesis, metabolic reprogramming, and cellular survival in hypoxic microenvironments, HIF signalling orchestrates adaptive responses, accelerating the unstoppable development of tumorous growth. Targeting several components of this cascade, including HIF-1, HIF-3, and FIH-1, MiR-210 plays a vital role in modifying HIF signalling and carefully controlling the HIF-mediated response and cellular fates in hypoxic environments. To understand the complexities of this relationship, careful investigation is required at the intersection of MiR-210 and HIF signalling. Understanding this relationship is crucial for uncovering the mechanisms underlying cancer aetiology and developing cutting-edge therapeutic approaches. The current review emphasises MiR-210's significance as a vital regulator of the HIF signalling cascade, with substantial implications spanning a range of tumor pathogenesis.

Pancreatic cancer stem cell-derived exosomal miR-210 mediates macrophage M2 polarization and promotes gemcitabine resistance by targeting FGFRL1.

Pancreatic cancer (PC) is a serious threat to human health, with most patients diagnosed at the advanced stages of the disease. Treatment with gemcitabine (GEM) leads to PC GEM resistance. In addition, cancer stem cell (CSC)-derived exosomes play an important role in cancer progression. We aimed to investigate the role and mechanism of action of PC stem cell-derived exosomes in PC drug resistance and progression. CSC-derived exosomes increased the proportion of F4/80+/CD86 + cells and levels of M2 polarization factors. miR-210 is expressed in CSC-derived exosomes. Thus, following co-culture, miR-210 was taken up by macrophages. Transfection or the addition of miR-210 mimics increased the proportion of F4/80+/CD206 + cells and levels of M2 polarization factors. Further, the miR-210 targets inhibited the levels of FGFRL1. The FGFRL1 overexpression plasmid also inhibited miR-210-mediated M2 polarization. After co-culture of THP-M2 cells with PC cells and treatment with GEM, the survival rate, migration rate, and levels of MDR, YB-1, BCRP, p-PI3K, p-AKT, and p-mTOR in PC cells increased. And THP-M2 increased the tumor volume and MDR, YB-1, BCRP, p-PI3K, p-AKT, and p-mTOR levels. Overall, miR-210 from PC stem cell-derived exosome targets and inhibits FGFRL1 to promote macrophage M2 polarization, which activates the p-PI3K/p-AKT/p-mTOR pathway and increases GEM resistance.

Expression of miR-210-3p in the aqueous humor of patients with age-related cataracts and its effect on human lens epithelial cell injury induced by hydrogen peroxide / Expressão de miR-210-3p no humor aquoso de pacientes com catarata relacionada à idade e seu efeito na lesão de células epiteliais do cristalino humano induzida por peróxido de hidrogênio

ABSTRACT Purpose: The regulatory effect of microRNA on diseases has been confirmed. This study aimed to evaluate the expression of microRNA-210-3p in age-related cataracts and assess the effect of abnormal miR-210-3p expressions on H2O2-induced SAR01/04 cells. Methods: Reverse-transcription quantitative polymerase chain reaction method was performed to assess the levels of miR-210-3p in aqueous humor samples. Receiver operating characteristic analysis was employed to assess the discrimination ability of miR-210-3p between patients with age-related cataracts and healthy people, and Pearson correlation analysis was used to identify the correlation between miR-210-3p and oxidative stress indices such as superoxide dismutase, glutathione peroxidase, malonaldehyde. Cell counting kit-8 assay and Transwell assay were used to estimate the biological function of H2O2-induced age-related cataract cell model. The levels of oxidative stress indices such as superoxide dismutase, glutathione peroxidase, and malonaldehyde were measured to evaluate the degree of oxidative stress damage in the age-related cataract cell model. The relationship between miR-210-3p and its target gene was verified by luciferase reporter gene analysis. Results: The miR-210-3p expression was elevated in the aqueous humor of patients with age-related cataracts. A high miR-210-3p expression showed a high diagnostic value for age-related cataracts and was significantly associated with the level of oxidative stress markers in patients with age-related cataracts. The inhibition of miR-210-3p can reverse oxidative stress stimulation and adverse effects on H2O2-induced cell function. Conclusions: The results suggested that miR-210-3p could promote cell viability, cell migration, and oxidative stress by targeting autophagy-related gene 7 in in vitro age-related cataract cell model.

RESUMO Objetivo: O efeito regulador do microRNA em doenças tem sido confirmado, e este artigo tentou avaliar a expressão do microRNA-210-3p na catarata relacionada à idade e avaliar o efeito da expressão anormal do miR-210-3p em células SAR01/04 induzidas por H2O2. Métodos: O método de transcrição reversa seguida de reação em cadeia da polimerase (RT-PCR) quantitativa foi realizado para avaliar os níveis de miR-210-3p em amostras de humor aquoso. Análise de características operacionais do receptor foi feita para avaliar a capacidade de discriminação do miR-210-3p entre pacientes com catarata relacionada à idade e pessoas saudáveis. A análise de correlação de Pearson identificou a correlação do miR-210-3p e índices de estresse oxidativo, como superóxido dismutase, glutationa peroxidase, malonaldeído. O ensaio de contagem de células kit-8 (cck-8) e o ensaio no sistema Transwell foram utilizados para estimar a função biológica do formato de células de catarata relacionada com a idade induzida por H2O2. Os níveis de índices de estresse oxidativo como superóxido dismutase, glutationa peroxidase e malonaldeído foram detectados para avaliar o grau de dano do estresse oxidativo em formato de células de catarata relacionada à idade. A relação entre miR-210-3p e seu gene alvo foi verificada por análise do gene repórter luciferase. Resultados: A expressão miR-210-3p foi elevada no humor aquoso de pacientes com catarata relacionada à idade. A expressão miR-210-3p altamente expressiva mostrou alto valor diagnóstico para catarata relacionada à idade e foi significativamente associado ao nível de marcadores de estresse oxidativo em pacientes com catarata relacionada à idade. A inibição de miR-210-3p pode reverter a estimulação do estresse oxidativo e os efeitos adversos da função celular induzida por H2O2. Conclusões: Esses dados sugeriram que a expressão miR-210-3p poderia promover a viabilidade celular, migração celular e estresse oxidativo ao direcionar genes ATG 7 relacionados à autofagia em modelo in vitro de células de catarata relacionadas à idade.

Alteration of circulating miRNAs during myocardial infarction and association with lipid levels.

BACKGROUND: Increasing mortality and morbidity of coronary artery disease (CAD) highlight the emerging need for novel noninvasive markers such as circulating microRNAs (miRNAs). OBJECTIVE: To evaluate the circulating levels of miR-126-3p, miR-210-3p, let-7g-5p, and miR-326, and their associations with known contributors to CAD, in CAD subgroups. METHODS: We divided the cohort into 4 groups: non-CAD controls (≤30% stenosis; n = 55), and patients with stable angina pectoris (SAP; n = 48), unstable AP (UAP; n = 46), and myocardial infarction (MI; n = 36). The circulating levels of miR-126-3p, miR-210-3p, let-7g-5p, and miR-326 were determined using TaqMan Advanced miRNA Assays in serum specimens. RESULTS: Circulating miR-126-3p levels were lower in the MI and UAP groups, compared with the non-CAD group, whereas miR-210-3p circulating levels were lower in the MI group than others. The levels of circulating let-7g-5p were shown to be useful for distinguishing UAP from MI, and there were substantial differences in circulating let-7g-5p levels between the UAP and MI groups. Moreover, lipid levels and ratios were lower in individuals with high circulating miR-126-3p and miR-210-3p levels. CONCLUSIONS: The study results suggest that circulating miR-126-3p, miR-210-3p, and let-7g-5p are differentiated between different clinical presentations of CAD and associated with lipid levels, which are important risk factors and determinants of CAD.

The miR-210 Primed Endothelial Progenitor Cell Exosomes Alleviate Acute Ischemic Brain Injury.

BACKGROUND: Stem cell-released exosomes (EXs) have shown beneficial effects on regenerative diseases. Our previous study has revealed that EXs of endothelial progenitor cells (EPC-EXs) can elicit favorable effects on endothelial function. EXs may vary greatly in size, composition, and cargo uptake rate depending on the origins and stimulus; notably, EXs are promising vehicles for delivering microRNAs (miRs). Since miR-210 is known to protect cerebral endothelial cell mitochondria by reducing oxidative stress, here we study the effects of miR-210-loaded EPC-EXs (miR210-EPC-EXs) on ischemic brain damage in acute ischemic stroke (IS). METHODS: The miR210-EPC-EXs were generated from EPCs transfected with miR-210 mimic. Middle cerebral artery occlusion (MCAO) surgery was performed to induce acute IS in C57BL/6 mice. EPC-EXs or miR210-EPC-EXs were administrated via tail vein injection 2 hrs after IS. To explore the potential mechanisms, inhibitors of the vascular endothelial growth factor receptor 2 (VEGFR2)/PI3 kinase (PI3K) or tyrosine receptor kinase B (TrkB)/PI3k pathways were used. The brain tissue was collected after treatments for infarct size, cell apoptosis, oxidative stress, and protein expression (VEGFR2, TrkB) analyses on day two. The neurological deficit score (NDS) was evaluated before collecting the samples. RESULTS: 1) As compared to EPC-EXs, miR210-EPC-EXs profoundly reduced the infarct volume and improved the NDS on day two post-IS. 2) Fewer apoptosis cells were detected in the peri-infarct brain of mice treated with miR210-EPC-EXs than in EPC-EXs-treated mice. Meanwhile, the oxidative stress was profoundly reduced by miR210-EPC-EXs. 3) The ratios of p-PI3k/PI3k, p- VEGFR2/VEGFR2, and p-TrkB/TrkB in the ipsilateral brain were raised by miR210-EPC-EXs treatment. These effects could be significantly blocked or partially inhibited by PI3k, VEGFR2, or TrkB pathway inhibitors. CONCLUSION: These findings suggest that miR210-EPC-EXs protect the brain from acute ischemia- induced cell apoptosis and oxidative stress partially through the VEGFR2/PI3k and TrkB/PI3k signal pathways.

LncRNA MIR210HG promotes the proliferation, migration, and invasion of lung cancer cells by inhibiting the transcription of SH3GL3.

Lung cancer (LCa), the most frequent malignancy worldwide, causes millions of mortalities each year. Overexpression of the long noncoding RNA MIR210HG in LCa has been established; however, a more comprehensive investigation into its biological role within LCa is imperative. This study aimed to validate the MIR210H levels in LCa tissues and cells. The expression of indicated genes was evaluated using quantitative real-time polymerase chain reaction (qRT-PCR) and/or Western blotting. The viability, proliferation, migration, and invasion of LCa cells were measured using the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), colony formation, wound healing, and transwell assays, respectively. The methylation levels of LCa cells were determined via methylation-specific PCR; additionally, chromatin immunoprecipitation or RNA immunoprecipitation assays were performed to determine the targeting relationship between DNA methyltransferase 1 (DNMT1) and the SH3-domain containing CRB2 like 3 (SH3GL3) promoters and the interaction between DNMT1 and MIR210HG, respectively. Our findings revealed the upregulation of MIR210HG, coupled with a diminished expression of SH3GL3 in LCa tissues and cells. Knockdown of MIR210HG or overexpression of SH3GL3 suppressed the proliferative, migratory, and invasive capacities of the cells. DNMT1 bound to the SH3GL3 promoter region, and MIR210HG inhibited the transcription of SH3GL3 by recruiting DNMT1. These findings indicate that MIR210HG facilitates LCa cell growth and metastasis by repressing SH3GL3 transcription via the recruitment of DNMT1 to the SH3GL3 promoter region.