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Although microRNAs (miRNAs/miRs) serve a significant role in the autophagy of vascular endothelial cells (ECs), the effect of miR­92a on the autophagy of ECs is currently unclear. Therefore, the present study aimed to investigate the impact of miR­92a on autophagy in ECs and the underlying molecular processes that control this biological activity. Firstly, an autophagy model of EA.hy926 cells was generated via treatment with the autophagy inducer rapamycin (rapa­EA.hy926 cells). The expression levels of miR­92a were then detected by reverse transcription­quantitative PCR, and the effect of miR­92a expression on the autophagic activity of rapa­EA.hy926 cells was studied by overexpressing or inhibiting miR­92a. The level of autophagy was evaluated by western blot analysis, immunofluorescence staining and transmission electron microscopy. Dual­luciferase reporter assays were used to confirm the interaction between miR­92a and FOXO3. The results demonstrated that the expression levels of miR­92a were decreased in the rapa­EA.hy926 cell autophagy model. Furthermore, overexpression and inhibition of miR­92a revealed that upregulation of miR­92a in these cells inhibited autophagy, whereas miR­92a knockdown promoted it. It was also confirmed that miR­92a directly bound to the 3'­untranslated region of the autophagy­related gene FOXO3 and reduced its expression. In conclusion, the present study suggested that miR­92a inhibits autophagy activity in EA.hy926 cells by targeting FOXO3.

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Subsequently to the publication of the above paper, an interested reader drew to the authors' attention that certain of the control western blotting data featured in Fig. 5 on p. 2581 had also appeared in a couple of other articles featuring several of the same authors [Tu K, Dou C, Zheng X, Li C, Yang W, Yao Y and Liu Q: Fibulin­5 inhibits hepatocellular carcinoma cell migration and invasion by down­regulating matrix metalloproteinase­7 expression. BMC Cancer 14: 938, 2014; and Gai X, Tu K, Li C, Roberts LR and Zheng X: Histone acetyltransferase PCAF accelerates apoptosis by repressing a GLI1/BCL2/BAX axis in hepatocellular carcinoma. Cell Death Dis 6: e1712, 2015]. In addition, the authors drew to the attention of the Editorial Office that a couple of mistakes were made during the assembly of Fig. 2D on p. 2579. The authors were able to re-examine their original data files, and realized that these figures had been inadvertently assembled incorrectly (they were also able to present the raw data from which these figures had been assembled to the Editorial Office). The revised versions of Figs. 2 and 5, containing the intended flow cytometric and western blotting data for these figures respectively, is shown on the next page. The authors wish to emphasize that the corrections made to these figures do not affect the overall conclusions reported in the paper, and they are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this corrigendum. All the authors agree to the publication of this corrigendum, and also apologize to the readership for any inconvenience caused. [Oncology Reports  34: 2576­2584, 2015; DOI: 10.3892/or.2015.4210].

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OBJECTIVE: As some articles have highlighted the role of microRNA-92a (miR-92a) in myocardial ischemia-reperfusion injury (MI/RI), this article aimed to investigate the effect of miR-92a on Sevoflurane (Sevo)-treated MI/RI via regulation of Krüppel-like factor 4 (KLF4). METHODS: An MI/RI rat model was established by ligating the left anterior descending coronary artery. The cardiac function, pathological changes of myocardial tissues, inflammatory response, oxidative stress and cardiomyocyte apoptosis in MI/RI rats were determined. KLF4 and miR-92a expression was detected in the myocardial tissue of rats, and the target relationship between miR-92a and KLF4 was confirmed. RESULTS: Sevo treatment alleviated myocardial damage, inflammatory response, oxidative stress response, and cardiomyocyte apoptosis, and improved cardiac function in MI/RI rats. miR-92a increased and KLF4 decreased in the myocardial tissue of MI/RI rats. KLF4 was targeted by miR-92a. Downregulation of miR-92a or upregulation of KLF4 further enhanced the effect of Sevo treatment on MI/RI. CONCLUSION: This study suggests that depletion of miR-92a promotes upregulation of KLF4 to improve cardiac function, reduce cardiomyocyte apoptosis and further enhance the role of Sevo treatment in alleviating MI/RI.

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Objective@#To explore the mechanism of advanced glycation end products (AGEs) on diabetic endothelial cell damage based on monocyte⁃macrophage exosomes (Exos)/microRNA⁃92a ( miR⁃92a) .@*Methods@#Twenty apolipoprotein E ⁃deficient (ApoE - / - ) mice were randomly divided into two groups : injury group (n = 10) and injury + STZ group ( n = 10 ) . The injury + STZ group established a diabetes model induced by streptozotocin (STZ) . All animals underwent partial left carotid artery (PLCA) ligation. The carotid arteries were collected , the number of M1 macrophages was detected by immunohistochemistry , and the level of AGEs was analyzed by ELISA.Microvascular endothelial cell line bEnd. 3 cells were treated with conditioned medium (CM) of AGEs treated RAW264. 7 cells or Exos derived from RAW264. 7 , followed by evaluations of the cell barrier function and mitochondrial function. @*Results @#There was an increased number of M1 macrophages in carotid atherosclerotic tissues of diabetic mice and in AGEs treated RAW264. 7 cells. CM or Exos significantly induced barrier dysfunction , reactive oxygen species (ROS) accumulation and mitochondrial dysfunction in vascular endothelial cells in vitro. In addition , bioinformatics analysis showed that miR⁃92a was up⁃regulated in Exos derived from macrophages stimulated by AGEs. Experimentally , Exos participated in CM⁃induced barrier dysfunction , ROS accumulation and mitochondrial dysfunction in bEnd. 3 cells by transferring miR⁃92a. Finally , a series of rescue experiments further confirmed that Exos regulated the barrier dysfunction and mitochondrial function in vascular endothelial cells through miR⁃92a.@*Conclusion@#The expression of AGEs and the number of M1 macrophages in diabetic ApoE - / - mice increase , and AGEs stimulates Exos from macrophages could impair the barrier function and mitochondrial function in vascular endothelial cells by delivering miR⁃92a in vitro.

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OBJECTIVE: This study attempted to investigate miR-92a-3p expression in peripheral blood of patients with severe ß-thalassemia, and the effect and action mechanism of miR-92a-3p on γ-globin expression and oxidative stress in erythroid precursor cells. METHODS: CD34+ hematopoietic progenitor cells (HPCs) were isolated from peripheral blood of healthy volunteers and patients with severe ß-thalassemia. The levels of miR-92a-3p, BCL11A, and γ-globin were measured in erythroid precursor cells. High-performance liquid chromatography (HPLC) was used to analyze hemoglobin F (HbF) content. HPCs were induced with erythroid differentiation and erythroid precursor cells were then obtained. The relevance between miR-92a-3p and BCL11A was studied using dual luciferase reporter gene assay, and the correlation between miR-92a-3p and HbF was assayed by Pearson correlation analysis. Reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) in erythroid precursor cells were tested to evaluate oxidative stress. Cell apoptosis was examined by flow cytometry. RESULTS: Remarkably higher expression of miR-92a-3p was observed in erythroid precursor cells. Increased expression of miR-92a-3p resulted in elevated levels of γ-globin, GSH, and SOD, reduced expression of ROS and MDA, and decreased cell apoptosis. BCL11A was identified as a target of miR-92a-3p and to be downregulated by miR-92a-3p. Moreover, BCL11A knockdown alone increased the expression of γ-globin, SOD and GSH, and repressed the levels of ROS and MDA and cell apoptosis, and the following inhibition of miR-92a-3p changed these patterns. CONCLUSIONS: Our data indicated that miR-92a-3p might increase γ-globin level and reduce oxidative stress and apoptosis in erythroid precursor cells by downregulating BCL11A.

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OBJECTIVE: Long non-coding RNA (lncRNA) essentially controls many physiological and pathological processes of deep vein thrombosis (DVT). Based on that, lncRNA taurine upregulated gene 1 (TUG1)-involved angiogenesis of endothelial progenitor cells (EPCs) and dissolution of DVT was explored. METHODS: In the in-vitro experiments, EPCs were engineered with mimic, inhibitor, siRNA, and plasmid, after which tube formation, proliferation, migration, and apoptosis were checked. In the in-vivo experiments, a DVT mouse model was established. Before the DVT operation, the mice were injected with agomir, antagomir, siRNA, and plasmid. Subsequently, thrombosis and damage to the femoral vein were pathologically evaluated. TUG1, miR-92a-3p, and 3-Hydroxy-3-methylglutaryl coenzyme A reductase (Hmgcr) expression in the femoral vein was tested. The relationship between TUG1, miR-92a-3p, and Hmgcr was validated. RESULTS: DVT mice showed suppressed TUG1 and Hmgcr expression, and elevated miR-92a-3p expression. In EPCs, TUG1 overexpression or miR-92a-3p inhibition promoted cellular angiogenesis, whereas Hmgcr silencing blocked cellular angiogenesis. In DVT mice, elevated TUG1 or inhibited miR-92a-3p suppressed thrombosis and damage to the femoral vein whilst Hmgcr knockdown acted oppositely. In both cellular and animal models, TUG1 overexpression-induced effects could be mitigated by miR-92a-3p up-regulation. Mechanically, TUG1 interacted with miR-92a-3p to regulate Hmgcr expression. CONCLUSION: Evidently, TUG1 promotes the angiogenesis of EPCs and dissolution of DVT via the interplay with miR-92a-3p and Hmgcr.

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Pulmonary fibrosis (PF) is a chronic lung disorder, in which the mechanism of mmu-microRNA (miR)-92a-3p is not elucidated clearly. The present work was proposed to disclose mmu-miR-92a-3p-focused mechanism in PF with cytoplasmic polyadenylation element-binding protein 4 (Cpeb4)/Smad2/3 axis. PF was induced in mice by the intratracheal injection of bleomycin (BLM). Then, the BLM-treated mice were injected with mmu-miR-92a-3p- and/or Cpeb4-related adenovirus vectors. mmu-miR-92a-3p, Cpeb4, and Smad2/3 expression in lung tissues were examined. Alveolar cell apoptosis and collagen deposition in lung tissues and inflammatory factors in serum were observed. The interaction between mmu-miR-92a-3p and Cpeb4 was explored. Lowly expressed mmu-miR-92a-3p and highly expressed Cpeb4 and Smad2/3 were manifested in BLM-induced PF mice. BLM-induced PF mice exhibited enhanced inflammation, alveolar cell apoptosis, and collagen deposition, which would be attenuated by upregulating mmu-miR-92a-3p or downregulating Cpeb4. mmu-miR-92a-3p targeted Cpeb4. Upregulating mmu-miR-92a-3p or downregulating Cpeb4 inactivated the Smad2/3 signaling pathway in BLM-induced PF mice. It is elaborated that mmu-miR-92a-3p attenuates the process of PF by modulating Cpeb4-mediated Smad2/3 signaling pathway, renewing the molecular mechanism of PF.

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Periodontitis is a chronic infectious disease that affects the oral health of adults. Long non-coding RNA OIP5 antisense RNA 1 (OIP5-AS1) has been reported to downregulated in the periodontal tissue of patients with periodontitis. Therefore, the study sought to look at the possible functions of OIP5-AS1 in periodontitis and the associated underlying mechanisms. In the present study, the expression level of OIP5-AS1 and microRNA-92a-3p were analyzed using reverse transcription-quantitative PCR. The levels of osteogenic proteins were determined using western blotting and inflammatory cytokines and oxidative stress were also examined. The proliferation of human periodontal ligament stem cells (hPDLSCs) was evaluated using MTT assays. Assay of osteogenic differentiation was undertaken by means of Alkaline phosphatase staining. The possible association between OIP5-AS1 and miR-92a-3p was determined applying dual-luciferase reporter assays and verified by RNA immunoprecipitation assay. We found that OIP5-AS1 was expressed at low levels in lipopolysaccharide (LPS)-stimulated hPDLSCs. OIP5-AS1 overexpression promoted proliferation and osteogenic differentiation ability and reduced LPS-induced inflammation in hPDLSCs. Furthermore, OIP5-AS1 directly targeted and reduced miR-92a-3p expression. The overexpression of miR-92a-3p partly abolished the effects of OIP5-AS1 on LPS-induced cell proliferation and osteogenic differentiation as well as inflammation in hPDLSCs. Collectively, the results indicated that OIP5-AS1 overexpression inhibited the LPS-induced inflammatory response and promoted the osteogenic differentiation of hPDLSCs by sponging miR-92a-3p. Thus, OIP5-AS1 is probably an essential objective for research during periodontitis treatment.

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OBJECTIVE: Recently, long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been identified as essential biomarkers during development of malignancies. This study was performed to study the roles of lncRNA opa-interacting protein 5 antisense transcript 1 (OIP5-AS1) and miR-92a in ovarian cancer (OC). METHODS: OIP5-AS1, miR-92a and integrin alpha 6 (ITGA6) expression in OC tissues and cells was assessed. The screened OC cells were respectively with OIP5-AS1-, miR-92a- and ITGA6-related vectors or oligonucleotides . The viability, migration, invasion and apoptosis of the cells were determined and the levels of epithelial-mesenchymal transition (EMT)-related proteins were also measured. The interactions between OIP5-AS1 and miR-92a, and between miR-92a and ITGA6 were confirmed. RESULTS: OIP5-AS1 and ITGA6 were upregulated while miR-92a was downregulated in OC. Inhibited OIP5-AS1 or downregulated ITGA6 or elevated miR-92a repressed EMT, viability, migration and invasion, and promoted apoptosis of OC cells. OIP5-AS1 as a competing endogenous RNA interacted with miR-92a to regulate ITGA6. These effects that induced by silenced OIP5-AS1 could be reversed by miR-92a inhibition while those that induced by up-regulated miR-92a were reduced by restored ITGA6. CONCLUSION: OIP5-AS1 silencing promoted miR-92a to repress proliferation and metastasis of OC cells through inhibiting ITGA6.

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Increasing long non-coding RNAs are reported to regulate the cell growth, apoptosis, and metastasis of cancer-associated fibroblasts (CAFs).This study aimed to explore how LINC01915 influences the conversion of normal fibroblasts (NFs) into CAFs in colorectal cancer (CRC). LINC01915 expression was initially measured in clinical tissue samples and in NFs and CAFs. Identification of the interaction between LINC01915, miR-92a-3p, KLF4, and CH25H was done. The effects of LINC01915, miR-92a-3p, and KLF4 on the angiogenesis, extracellular vesicle (EV) uptake by NFs, and activation of stromal cells were assessed using gain- or loss-of-function approaches. Xenograft mouse models were established to validate these in vitro findings in vivo. EVs were shown to stimulate NF proliferation, migration, and angiogenesis, as well as facilitate NF conversion into CAFs. CRC tissues and CAFs showed downregulated expression of LINC01915, which was associated with poor prognosis of patients. Moreover, employed LINC01915 inhibited tumor angiogenesis, CAF activation, and the uptake of tumor-derived EVs by NFs. Mechanistically, LINC01915 could competitively bind to miR-92a-3p and caused upregulation of the miR-92a-3p target KLF4 which, in turn, promoted the transcription of CH25H, leading to the suppressed uptake of EVs by NFs. The in vivo and in vitro experimental results showed that LINC01915 inhibited the uptake of CRC-derived EVs by NFs through the miR-92a-3p/KLF4/CH25H axis, thus arresting the angiogenesis and the conversion of NFs into CAFs and in turn prevent tumor growth. These data together supported the inhibiting role of LINC01915 in the conversion of NFs into CAFs triggered by the CRC-derived EVs and the ensuing tumor growth, which may be related to its regulation on the miR-92a-3p/KLF4/CH25H axis.

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OBJECTIVE: To analyze the correlation of the expression of microRNA-92a (miR-92a), microRNA-224 (miR-224), and microRNA-25 (miR-25) in non-small cell lung cancer with its clinical characteristics. METHODS: This prospective study was performed in 125 non-small cell lung cancer patients admitted to our hospital between January 2019 and January 2020. All patients' cancer and adjacent tissue were collected and the expression of miR-92a, miR-224, and miR-25 were detected using real-time fluorescence quantitative RT-PCR. Data were analyzed using SPSS statistical software (version 20.0). Correlation analysis was conducted using Pearson correlation coefficient. RESULTS: Compared with adjacent tissue, the relative expression of miR-92a, miR-224, and miR-25 in cancer tissue were increased (all P<0.001). There was no correlation between the expression of miR-92a, miR-224, and miR-25 and baseline data like gender, age, smoking history, and tumor size (all P>0.05). The relative expression of miR-92a, miR-224 and miR-25 in differentiated cancer patients were higher than those in highly and moderately differentiated cancer patients (all P<0.05). The relative expression of miR-92a, miR-224 and miR-25 in patients with lymph node metastasis (LNM) were increased when compared with those had no LNM (all P<0.001). Compared with stage I and II patients, the relative expression of miR-92a, miR-224 and miR-25 in stage III and IV patients were increased (all P<0.001). The relative expression of miR-92a, miR-224, and miR-25 were positively correlated to each other (all P<0.01). CONCLUSION: miR-92a, miR-224, and miR-25 are overexpressed in non-small cell lung cancer and the expressions are related to the degree of differentiation, presence or absence of LNM, and TNM staging. In addition, the expression of miR-92a, miR-224 and miR-25 are positively correlated to each other. This suggests that miR-92a, miR-224, and miR-25 cooperatively participated in the occurrence and development of non-small cell lung cancer.

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Blood brain barrier (BBB) dysfunction developed with aging is related to brain microvascular endothelial cells (BMECs) injury and losses of tight junctions (TJs). In the present study, we found that Alisol A 24-acetate (AA), a natural compound frequently used as treatment against vascular diseases was essential for BMECs injury and TJs degradation. Our experimental results showed that AA enhanced cell viability and increased zonula occludens-1 (ZO-1), claudin-5, and occludin expression in the oxygen-glucose deprivation (OGD)-induced BMECs. The exploration of the underlying mechanism revealed that AA restrained miR-92a-3p, a noncoding RNA involved in endothelial cells senescence and TJs impairment. To test the role of the miR-92a-3p in BMECs, the cells were transfected with miR-92a-3p mimics and inhibitor. The results showed that miR-92a-3p mimics inhibited cell viability and elevated lactate dehydrogenase (LDH) levels as well as suppressed ZO-1, claudin-5 and occludin expression, while the miR-92a-3p inhibitor reversed the above results. These findings were similar to the therapeutic effects of AA in the OGD-induced BMECs. Bioinformatics analysis and dual-luciferase assay confirmed ZO-1 and occludin were the target genes of miR-92a-3p mediated AA protective roles. In summary, the data demonstrated that AA protected against BMECs damage and TJs loss through the inhibition of miR-92a-3p expression. This provided evidence for AA application in aging-associated BBB protection.

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PURPOSE: Atherosclerosis and its related clinical complications are the leading cause of death. MicroRNA (miR)-92a in the inflammatory endothelial dysfunction leads to atherosclerosis. Krüppel-like factor 2 (KLF2) is required for vascular integrity and endothelial function maintenance. Flavonoids possess many biological properties. This study investigated the vascular protective effects of chrysin in balloon-injured carotid arteries. MATERIALS AND METHODS: Exosomes were extracted from human coronary artery endothelial cell (HCAEC) culture media. Herb flavonoids and chrysin were the treatments in these atheroprotective models. Western blotting and real-time PCRs were performed. In situ hybridization, immunohistochemistry, and immunofluorescence analyses were employed. RESULTS: MiR-92a increased after balloon injury and was present in HCAEC culture media. Chrysin was treated, and significantly attenuated the miR-92a levels after balloon injury, and similar results were obtained in HCAEC cultures in vitro. Balloon injury-induced miR-92a expression, and attenuated KLF2 expression. Chrysin increased the KLF2 but reduced exosomal miR-92a secretion. The addition of chrysin and antagomir-92a, neointimal formation was reduced by 44.8 and 49.0% compared with balloon injury after 14 days, respectively. CONCLUSION: Chrysin upregulated KLF2 expression in atheroprotection and attenuated endothelial cell-derived miR-92a-containing exosomes. The suppressive effect of miR-92a suggests that chrysin plays an atheroprotective role. Proposed pathway for human coronary artery endothelial cell (HCAEC)-derived exosomes induced by chrysin to suppress microRNA (miR)-92a expression and counteract the inhibitory effect of miR-92a on KLF2 expression in HCAECs. This provides an outline of the critical role of the herbal flavonoid chrysin, which may serve as a valuable therapeutic supplement for atheroprotection.

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CONTEXT: Alisol A 24-acetate has been used to treat vascular diseases. However, the underlying mechanisms still remain unclear. OBJECTIVE: The present study evaluated the antiapoptotic effect of alisol A 24-acetate on brain microvascular endothelial cells (BMECs) and explored the underlying mechanisms. MATERIALS AND METHODS: BMECs were injured through oxygen -glucose deprivation (OGD) after alisol A 24-acetate treatment. Cell viability and half-maximal inhibitory concentration (IC50) were measured using CCK-8, whereas inflammatory factors and oxidative stress indicators were measured using enzyme linked immunosorbent assay. Cell invasion and wound healing assays were detected. Cell apoptosis was assessed using flow cytometry. B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X (Bax) expression were analyzed using Western blotting. Dual-luciferase assay was applied to detect target genes of miR-92a-3p. RESULT: Alisol A 24-acetate had an IC50 of 98.53 mg/L and inhibited cell viability at concentrations over 50mg/L. OGD induced apoptosis and promoted miR-92a-3p overexpression in BMECs. However, alisol A 24-acetate treatment suppressed inflammation, improved migration and invasion abilities, increased Bcl-2 expression, inhibited Bax expression, and repressed apoptosis and miR92a-3p overexpression in OGD-induced BMECs. MiR-92a-3p overexpression promoted cell apoptosis and suppressed Bcl-2 expression, whereas its inhibitor reversed the tendency. Alisol A 24-acetate treatment relieved the effects of miR-92a-3p overexpression. Dual-luciferase assay confirmed that miR-92a-3p negatively regulated the Bcl-2 expression. CONCLUSIONS: These findings suggest that alisol A 24-acetate exerts antiapoptotic effects on OGD-induced BMECs through miR-92a-3p inhibition by targeting the Bcl-2 gene, indicating its potential for BMECs protection and as a novel therapeutic agent for the treatment of cerebrovascular disease.

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Localized stimulation of angiogenesis is an attractive strategy to improve the repair of ischemic or injured tissues. Several microRNAs (miRNAs) such as miRNA-92a (miR-92a) have been reported to negatively regulate angiogenesis in ischemic disease. To exploit the clinical potential of miR-92a inhibitors, safe and efficient delivery needs to be established. Here, we used deoxycholic acid-modified polyethylenimine polymeric conjugates (PEI-DA) to deliver a locked nucleic acid (LNA)-based miR-92a inhibitor (LNA-92a) in vitro and in vivo. The positively charged PEI-DA conjugates condense the negatively charged inhibitors into nano-sized polyplexes (135 ± 7.2 nm) with a positive net charge (34.2 ± 10.6 mV). Similar to the 25 kDa-branched PEI (bPEI25) and Lipofectamine RNAiMAX, human umbilical vein endothelial cells (HUVECs) significantly internalized PEI-DA/LNA-92a polyplexes without any obvious cytotoxicity. Down-regulation of miR-92a following the polyplex-mediated delivery of LNA-92a led to a substantial increase in the integrin subunit alpha 5 (ITGA5), the sirtuin-1 (SIRT1) and Krüppel-like factors (KLF) KLF2/4 expression, formation of capillary-like structures by HUVECs, and migration rate of HUVECs in vitro. Furthermore, PEI-DA/LNA-92a resulted in significantly enhanced capillary density in a chicken chorioallantoic membrane (CAM) model. Localized angiogenesis was substantially induced in the subcutaneous tissues of mice by sustained release of PEI-DA/LNA-92a polyplexes from an in situ forming, biodegradable hydrogel based on clickable poly(ethylene glycol) (PEG) macromers. Our results indicate that PEI-DA conjugates efficiently deliver LNA-92a to improve angiogenesis. Localized delivery of RNA interference (RNAi)-based therapeutics via hydrogel-laden PEI-DA polyplex nanoparticles appears to be a safe and effective approach for different therapeutic targets.

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OBJECTIVE: Histone deacetylases (HDACs) have been revealed to be involved in cerebrovascular diseases, while the role of HDAC9 in intracranial aneurysm (IA) remains seldom studied. We aim to explore the role of the HDAC9/microRNA-92a (miR-92a)/Bcl-2-like protein 11 (BCL2L11) axis in IA progression. METHODS: Expression of HDAC9, miR-92a and BCL2L11 in IA tissues was assessed. IA rat models were established by ligation of left renal artery and common carotid artery, and the rats were respectively injected with relative plasmid vectors and/or oligonucleotides. The blood pressure was measured to estimate the IA degree, and the pathological changes were observed. The expression of matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor (VEGF) was detected, and the levels of inflammatory factors were evaluated. Expression of apoptosis-related proteins, HDAC9, miR-92a and BCL2L11 was assessed. RESULTS: HDAC9 and BCL2L11 were upregulated while miR-92a was downregulated in IA clinical samples and rat models. HDAC9 inhibition or miR-92a elevation improved pathological changes and repressed apoptosis and expression of MMP-2, MMP-9, VEGF and inflammatory factors in vascular tissues from IA rats. Oppositely, HDAC9 overexpression or miR-92a reduction had contrary effects. miR-92a downregulation reversed the effect of silenced HDAC9 on IA rats. CONCLUSION: HDAC9 inhibition upregulates miR-92a to repress the progression of IA via silencing BCL2L11.

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MicroRNA (miRNA/miR)­92a has been identified as being significantly downregulated in non­small cell lung cancer (NSCLC) tissues using a miRNA array. However, its biological function and molecular mechanisms in NSCLC have not been fully elucidated. The aim of the present study was to determine the role of miR­92a in NSCLC and the mechanisms by which it affects NSCLC cells. The expression levels of miR­92a in NSCLC tissues and cell lines were analyzed using reverse transcription­quantitative PCR. Cell viability and cell apoptosis were determined using an MTT assay and flow cytometry, respectively. It was observed that miR­92a was significantly upregulated in NSCLC tissues and cell lines. Inhibition of miR­92a significantly suppressed viability of NSCLC cells, with concomitant downregulation of key proliferative genes, such as proliferating cell nuclear antigen and Ki­67. miR­92a downregulation induced apoptosis of NSCLC cells, as evidenced by flow cytometry and apoptosis­related protein detection. Luciferase assays confirmed that miR­92a could directly bind to the 3'­untranslated region of tumor suppressor F­box/WD repeat­containing protein 7 (FBXW7) and suppress its translation. Furthermore, small interfering RNA­mediated FBXW7 inhibition partially attenuated the tumor suppressive effect of an miR­92a inhibitor on NSCLC cells. Collectively, these findings demonstrated that miR­92a might function as an oncogene in NSCLC by regulating FBXW7. In conclusion, miR­92a could serve as a potential therapeutic target in NSCLC treatment.

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The aim of the present study was to investigate the role of miR-92a in lipid metabolism in hypoxic rats. Microarray analysis and reverse transcription-quantitative (RT-q)PCR were used to detect changes in the mRNA expression levels of miR-92a in the epididymal fat of hypoxic and normoxic rats. The downstream target mRNA of miR-92a was predicted using bioinformatics analysis and verified using a dual luciferase reporter assay. Changes in the expression of frizzled (Fzd)10 and c-Myc in the epididymal fat were detected using RT-qPCR and western blotting. Microarray analysis and RT-qPCR results showed that the expression of miR-92a was significantly lower in the fat tissues of the hypoxic rats compared with the normoxic rats. The results of the dual luciferase reporter assay showed that the target gene of miR-92a was Fzd10, which is an acceptor in the Wnt pathway. Fzd10 expression was upregulated in the hypoxic rats. The mRNA expression levels of c-Myc, which is located downstream of the Wnt pathway, was increased significantly. The increase in the mRNA and protein expression levels of Fzd10 and c-Myc may be associated with miR-92a downregulation. Downregulation of miR-92a in-turn may result in lipolysis through the regulation of the Wnt/ß-catenin signaling pathway, and thus weight loss in the rats.

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BACKGROUND: Early diagnosis of asymptomatic carotid artery stenosis (ACAS) is important to prevent the incidence of cerebrovascular events. This study aimed to investigate the circulating expression of microRNA-92a (miR-92a) in ACAS patients and evaluate its diagnostic value for ACAS and predictive value for cerebrovascular events. METHODS: Circulating expression of miR-92a was measured using quantitative real-time PCR. Chi-square test was used to analyze the association of miR-92a with ACAS patients' clinical characteristics. A receiver operating characteristic (ROC) was used to evaluate the diagnostic value of miR-92a, and the Kaplan-Meier method and Cox regression analysis were used to assess the predictive value of miR-92a for cerebrovascular events. RESULTS: Serum expression of miR-92a was higher in ACAS patients than that in the healthy controls (P <  0.001), and associated with patients' degree of carotid stenosis (P = 0.013). The elevated miR-92a expression could distinguish ACAS patients from healthy individual, and was an independent predictive factor for the occurrence of cerebrovascular events (P = 0.015). CONCLUSION: The data from this study indicated that circulating increased miR-92a may serve as a noninvasive diagnostic biomarker for ACAS and a potential risk factor for the future onset of cerebrovascular events.

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The aim of this study is to   investigate the effect of miRNA-92a on GC cell proliferation, migration and invasiveness, and the mechanism(s) involved.  Four GC cell lines (SGC-7901, BGC-823, MKN45 and HGC-27) and normal human gastric epithelial cells (GES1) were used in this study. MicroRNA-92a mimics or inhibitor were transfected into the cells. The results of transfection were assessed using real-time quantitative polymerase chain reaction (qRT-PCR). Cell proliferation, migration, invasiveness and apoptosis were determined using cell counting kit 8 (CCK-8), scratch test, Transwell invasion assay, and flow cytometric analysis, respectively. The protein target of miRNA-92a was predicted using Bioinformatics. The expression of FOXO1 protein was measured using Western blotting. The expression of miRNA-92a was significantly upregulated in GC cells, relative to normal gastric epithelial cells (p < 0.05). Overexpression of miRNA-92a significantly promoted the proliferation, migration and invasiveness of GC cells, but significantly inhibited their apoptosis (p < 0.05). MicroRNA-92a directly targeted FOXO1 gene, and significantly reduced its protein expression. Overexpression of miRNA-92a promotes the proliferation, migration and invasiveness of GC cells, and plays a role similar to that of oncogene. It directly targets FOXO1 gene by inhibiting its protein expression.

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