Function Of miR-21 Research Articles

MicroRNA-21 Contributes to Cutaneous Squamous Cell Carcinoma Progression via Mediating TIMP3/PI3K/AKT Signaling Axis.

BackgroundThough the therapeutic potentials of microRNAs (miRNAs) are extensively explored in cutaneous squamous cell carcinoma (CSCC), the concrete function of miR-21 in this disorder has not been thoroughly comprehended. Therein, this work is launched to clarify the miR-21-pivoted mechanism in CSCC from the perspective of tissue inhibitor of metalloproteinases-3 (TIMP3) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway.MethodsMicroarray-based analysis was utilized to screen out miR-21 with the most up-regulated expression in CSCC tissues. The relation between miR-21 and TIMP3 expression in tissues, and the overall survival of CSCC patients was evaluated. Loss-of-function assays were performed in cells to explore the independent and combined functions of miR-21 and TIMP3 in CSCC cell progression. Mice were injected with miR-21 inhibitor or TIMP3 si for identifying their roles in tumor formation and liver metastasis. The mechanism among miR-21, TIMP3 and PI3K/AKT pathway was interpreted.ResultsMiR-21 was up-regulated while TIMP3 was down-regulated in CSCC tissues, which were connected with unsatisfactory survival of patients. Down-regulating miR-21 inhibited CSCC cell progression and retarded CSCC tumor formation and metastasis in mice. Silencing of TIMP3 reversed the effects of miR-21 down-regulation on CSCC progression. Besides, down-regulating miR-21 inhibited PI3K/AKT pathway activation in CSCC cells via mediating TIMP3.ConclusionIt is elucidated that miR-21 depletion impedes CSCC cell invasion and metastasis via enhancing TIMP3 and suppressing PI3K/AKT pathway activation.

Circ01592 regulates unsaturated fatty acid metabolism through adsorbing miR-218 in bovine mammary epithelial cells.

The composition of fatty acids plays a key role in regulating milk flavor and quality. Therefore, to improve the quality of milk, it is particularly important to study the regulatory mechanism of fatty acid metabolism in dairy cows. In this study, the expression profiles at non-lactation, peak-lactation, mid-lactation and late-lactation were constructed by high-throughput sequencing. Considering non-lactation as the control group and the other points as the experimental groups, the differentially expressed genes were screened. ELOVL5 was significantly upregulated and was selected for subsequent analyses. Bioinformatics prediction, a dual-luciferase assay, qPCR analysis and western blot analysis were used for verification. The results showed that ELOVL5 was a downstream target gene of miR-218 that regulated milk fat metabolism. A dual-luciferase assay and expression level analysis showed that circ01592 can directly bind to miR-218 and that overexpression of circ01592 (pcDNA-circ01592) significantly reduced the expression of miR-218 and enhanced the expression of ELOVL5, the target gene of miR-218 in BMECs. A functional study of BMECs showed that circ01592 promoted the synthesis of TAG and increased the content of UFA. The function of miR-218 was opposite to that of circ01592. Overall, the data showed that circ01592 promoted TAG synthesis and fatty acid composition by binding miR-218, alleviating the inhibitory effect of miR-218 on ELOVL5 expression. These mechanisms provide a new research approach and theoretical basis for improving milk quality.

Prognostic markers for severity, activity, and recurrence of alopecia areata

Background Alopecia areata (AA) is considered an autoimmune disorder caused by altered T-cell-mediated immunity. MicroRNAs (miR) are important translational regulators of genes in various tissues and biological processes involved in autoimmune responses and have been identified in autoimmune diseases such as rheumatoid arthritis and type I diabetes mellitus. However, little is known about their role in pathogenesis of AA.Objective To assess serum levels of miR-155 and miR-146a in patients with AA and to correlate them with different clinical variables. Patients and methods MiR-155 and miR-146a serum levels were identified by real-time PCR in 50 patients with AA and 50 healthy age-matched and sex-matched patients as controls. Disease severity in the patients was assessed by Severity of Alopecia Tool score. Results There was a statistically significant increase in serum miR-155 and miR-146a levels in patients with AA than in controls. A significant increase in serum levels of miR-155 was found in patients with active disease and recurrent lesions of AA, whereas significant increase in serum level of miR-146a was found in patients with recurrent disease only. Significant positive correlations were found between serum miR-155 and miR-146a levels and disease severity. Conclusion Serum levels of miR-155 and miR-146a seem to have an essential role in the etiopathogenesis of AA and could be markers for severity and early detection of recurrent AA. In addition, serum miR-155 could be a marker of activity in AA, whereas serum miR-146a could be a marker of multiplicity. Further understanding of the function and regulation of miR-155 and miR-146a could be of great value for the introduction of new therapeutic approaches for AA.

MiR-137 overexpression protects neurons from Aβ-induced neurotoxicity via ERK1/2

Accumulation of amyloid-β (Aβ) is implicated in the pathogenesis and development of Alzheimer's disease (AD) and it is a prime suspect for causing neuronal loss and cognitive deficits during AD. To explore the mechanisms of Aβ-induced neurodegeneration, we used Aβ-treated primary cortical neuron culture as a cell model of AD and investigated the function of miR-137 in this process. qRT-PCR and western blot were used to examine levels of miR-137, AMPA receptors (AMPARs), p-ERK1/2, and ERK1/2. MTT assay and caspases 3 activity assay were employed to examine cell viability and apoptosis. Dual-luciferase assay was used to validate the interaction between miR-137 and ERK1/2. We found that Aβ decreased cell viability, AMPAR and miR-137 levels, but increased caspase 3 activity in a dose- and time-dependent manner. Overexpression of miR-137 suppressed the Aβ-induced neurotoxicity. MiR-137 directly bound to ERK1/2 mRNA and negatively regulated its expression. Further, overexpression of ERK1/2 blocked the effects of miR-137 mimics on Aβ-induced neurotoxicity. These results provide strong evidence that miR-137 protects neurons against Aβ-induced neurotoxicity via targeting ERK1/2.

RNA-binding proteins La and HuR cooperatively modulate translation repression of PDCD4 mRNA

Posttranscriptional regulation of gene expression plays a critical role in controlling the inflammatory response. An uncontrolled inflammatory response results in chronic inflammation, often leading to tumorigenesis. Programmed cell death 4 (PDCD4) is a proinflammatory tumor-suppressor gene which helps to prevent the transition from chronic inflammation to cancer. PDCD4 mRNA translation is regulated by an interplay between the oncogenic microRNA miR-21 and the RNA-binding protein (RBP) human antigen R (HuR) in response to lipopolysaccharide stimulation, but the role of other regulatory factors remains unknown. Here, we report that the RBP lupus antigen (La) interacts with the 3ʹ-untranslated region of PDCD4 mRNA and prevents miR-21-mediated translation repression. While lipopolysaccharide causes nuclear-cytoplasmic translocation of HuR, it enhances cellular La expression. Remarkably, La and HuR were found to bind cooperatively to the PDCD4 mRNA and mitigate miR-21-mediated translation repression. The cooperative action of La and HuR reduced cell proliferation and enhanced apoptosis, reversing the pro-oncogenic function of miR-21. Together, these observations demonstrate a cooperative interplay between two RBPs, triggered differentially by the same stimulus, which exerts a synergistic effect on PDCD4 expression and thereby helps maintain a balance between inflammation and tumorigenesis.

From miRNA Target Gene Network to miRNA Function: miR-375 Might Regulate Apoptosis and Actin Dynamics in the Heart Muscle via Rho-GTPases-Dependent Pathways.

MicroRNAs (miRNAs) are short, single-stranded, non-coding ribonucleic acid (RNA) molecules, which are involved in the regulation of main biological processes, such as apoptosis or cell proliferation and differentiation, through sequence-specific interaction with target mRNAs. In this study, we propose a workflow for predicting miRNAs function by analyzing the structure of the network of their target genes. This workflow was applied to study the functional role of miR-375 in the heart muscle (myocardium), since this miRNA was previously shown to be associated with heart diseases, and data on its function in the myocardium are mostly unclear. We identified PIK3CA, RHOA, MAPK3, PAFAH1B1, CTNNB1, MYC, PRKCA, ERBB2, and CDC42 as key genes in the miR-375 regulated network and predicted the possible function of miR-375 in the heart muscle, consisting mainly in the regulation of the Rho-GTPases-dependent signaling pathways. We implemented our algorithm for miRNA function prediction into a Python module, which is available at GitHub.

Revealing Epigenetic Factors of circRNA Expression by Machine Learning in Various Cellular Contexts.

SummaryCircular RNAs (circRNAs) have been identified as naturally occurring RNAs that are highly represented in the eukaryotic transcriptome. Although a large number of circRNAs have been reported, the underlying regulatory mechanism of circRNAs biogenesis remains largely unknown. Here, we integrated in-depth multi-omics data including epigenome, transcriptome, and non-coding RNA and identified candidate circRNAs in six cellular contexts. Next, circRNAs were divided into two classes (high versus low) with different expression levels. Machine learning models were constructed that predicted circRNA expression levels based on 11 different histone modifications and host gene expression. We found that the models achieve great accuracy in predicting high versus low expressed circRNAs. Furthermore, the expression levels of host genes of circRNAs, H3k36me3, H3k79me2, and H4k20me1 contributed greatly to the classification models in six cellular contexts. In summary, all these results suggest that epigenetic modifications, particularly histone modifications, can effectively predict expression levels of circRNAs.

MiR-9 and the Midbrain-Hindbrain Boundary: A Showcase for the Limited Functional Conservation and Regulatory Complexity of MicroRNAs

MicroRNAs regulate gene expression at post-transcriptional levels. Some of them appear to regulate brain development and are involved in neurodevelopmental disorders. This has led to the suggestion that the role of microRNAs in neuronal development and function may be more central than previously appreciated. Here, we review the data about miR-9 function to depict the subtlety, complexity, flexibility and limited functional conservation of this essential developmental regulatory system. On this basis we propose that species-specific actions of miR-9 could underlie to a large degree species differences in brain size, shape and function.

MiR-214 sensitizes human colorectal cancer cells to doxorubicin by p53 targeting

Objectives: This study aimed to investigate the potential function of miR-214 in the apoptosis induction by targeting p53 in human colorectal cancer cells (CRC) in combination with doxorubicin (DOX). Methods: miR-214 mimics were transfected to HT-29 CRC cells. Following that, the transfected cells were treated with DOX. Cell viability, apoptosis, and migration were evaluated by MTT, flow cytometry, and scratch-wound motility assays, respectively. Furthermore, the expression level of miR-214 and p53 was evaluated by qRT-PCR. Results: miR-214 transfection significantly inhibited the cell proliferation rate (P<0.05), induced apoptosis (P<0.05), and harnessed migration (P<0.05) in the HT-29 cells after 48 h. Furthermore, more effectiveness was observed in combination with DOX. Additionally, miR-214 transfection led to a reduction in p53 expression offering that it might be a potential target for miR-214. Conclusion: In conclusion, miR-214 sensitizes HT-29 cells to doxorubicin by targeting p53 indicating the significant role of this miRNA in colorectal cancer chemotherapy.

Synergism of HPV and MNNG repress miR-218 promoting Het-1A cell malignant transformation by targeting GAB2

Dysregulation of microRNAs (miRNAs) is induced during tumorigenesis. Our previous research suggested that HPV and MNNG led to malignant transformation of esophageal epithelial cells. To investigate the regulation and function of miR-218(miR-218-5p) during the malignant transformation of esophageal epithelial cells, we found miR-218 was inhibited synergistically by HPV and MNNG, suppressing cell proliferation, migration and invasion by up-regulating 3′ untranslated region (3′UTR) GAB2 in Het-1A-HPV-MNNG cells (malignant Het-1A cells induced by HPV and MNNG). A negative correlation was found between miR-218 and GAB2 mRNA expression in esophageal cancer patients and control people. GAB2 was up-regulated in Het-1A-HPV-MNNG cells. Further, down-expression of GAB2 reversed HPV&MNNG-mediated activation of migration and invasion and repressed SHP2/ERK and Akt/mTOR pathway signaling. In conclusion, miR-218 partially accounts for the prevention effect during malignant transformation of normal esophageal epithelial cells, which targets GAB2, which supplies the potential treatment in cancer therapy.

MiRNA-145 and Its Direct Downstream Targets in Digestive System Cancers: A Promising Therapeutic Target.

MicroRNAs (miRNAs) play a vital role in the onset and development of many diseases, including cancers. Emerging evidence shows that numerous miRNAs have the potential to be used as diagnostic biomarkers for cancers, and miRNA-based therapy may be a promising therapy for the treatment of malignant neoplasm. MicroRNA-145 (miR-145) has been considered to play certain roles in various cellular processes, such as proliferation, differentiation and apoptosis, via modulating the expression of direct target genes. Recent reports show that miR-145 participates in the progression of digestive system cancers, and plays crucial and novel roles in cancer treatment. In this review, we summarize the recent knowledge concerning the function of miR-145 and its direct targets in digestive system cancers. We discuss the potential role of miR-145 as a valuable biomarker for digestive system cancers and how miR-145 regulates these digestive system cancers via different targets to explore the potential strategy of targeting miR-145.

Methylation-Mediated Silencing of MicroRNA-497 Promotes Breast Cancer Progression Through Up-Regulation of Mucin1.

BackgroundPotential anti-tumor effects of microRNA-497 (miR-497) have been highlighted in various malignancies including breast cancer. However, little is known about the function of miR-497 and its putative target mucin1 (MUC1) in breast cancer. The present study explored how miR-497 regulates breast cancer progression in a MUC1-dependent manner.MethodsExpression of miR-497 and MUC1 was determined in breast cancer tissues and cells. Methylation specific polymerase chain reaction was used to measure the methylation status of CpG islands of miR-497 promoter, while chromatin immunoprecipitation assay was used to detect recruitment of methyltransferase to the promoter region of miR-497. Alteration in expression of miR-497 (overexpression) and MUC1 (up- and down-regulation) was performed to examine their roles in breast cancer biology in vitro and in vivo. The binding affinity between miR-497 and MUC1 was investigated through a bioinformatics database and dual luciferase reporter gene assay.ResultsMiR-497 was down-regulated and MUC1 was up-regulated in breast cancer tissues and cell lines. Besides, methylation induced a down-regulation of miR-497 in breast cancer. The bioinformatics analysis and dual luciferase reporter gene assay indicated that miR-497 targeted MUC1. Overexpression of miR-497 inhibited breast cancer cell proliferation and invasion and promoted the apoptosis of breast cancer cells by down-regulating MUC1. The inhibitory action of miR-497 on tumor growth was validated in vivo.ConclusionIn conclusion, miR-497 down-regulated MUC1 expression and subsequently suppressed breast cancer progression, highlighting miR-497 to be a potential biomarker and therapeutic target for breast cancer therapy.

MicroRNA-145 targets in cancer and the cardiovascular system: evidence for common signaling pathways.

miRNAs are small regulatory RNAs which govern gene expression post-transcriptionally by primarily binding to the 3'-UTR of mRNA target genes. miR-145 is a well-studied miRNA that has been implicated in controlling a range of biological processes. miR-145 is expressed in a variety of tissues and cell types and acts as a tumor-suppressor by regulating target gene signaling pathways involved in different aspects of tumor growth and progression. There is also strong evidence that highlights the important functions of miR-145 in the cardiovascular system. Here, we review the mechanisms of miR-145 in tumorigenesis and cancer progression and compare and contrast with the roles of miR-145 in cardiovascular development and disease. We discuss the important targets of miR-145 in cancer and their possible link to the cardiovascular system.

Overexpression of neural miRNAs miR-9/9* and miR-124 suppresses differentiation to Müller glia and promotes differentiation to neurons in mouse retina in vivo.

MicroRNAs (miRNAs) are known to regulate gene expression and modulate cellular differentiation. MicroRNA-9/9* (miR-9/9*) and microRNA-124 (miR-124) are highly expressed in the central nervous system. In vivo function of miR-9/9* and miR-124 has been investigated in detail, whereas there remain some discrepancies regarding neural development. To this end, we electroporated miR-9/9*, miR-124 or miR-9/9*/124 expression plasmids into neonatal retinal progenitor cells (RPCs) in vivo and analyzed the fate of electroporated cells. Both miR-9/9* and miR-124 reduced the number of SOX9- and GS-positive cells and increased that of TUBB3-positive cells in the postnatal day 14 retina. No major effects on the proliferation and apoptosis of the electroporated cells were detected at least postnatal day 3. These indicated that miR-9/9* and miR-124 influence the cell fate of glial cells, thereby inducing their differentiation into neurons. Moreover, we found this cell fate modulation was occurred in RPCs indicating high-level expression of miRNA, but not in the low level. Our results strongly suggest that high-level miRNA overexpression is essential for directing cell fate by miR-9/9* and miR-124 interference.

Exosome-Encapsulated MicroRNA-21 from Esophageal Squamous Cell Carcinoma Cells Enhances Angiogenesis of Human Umbilical Venous Endothelial Cells by Targeting SPRY1.

ObjectiveEsophageal squamous cell carcinoma (ESCC) persists among the most prevalent cancers worldwide. Angiogenesis represents a crucial element necessitated for tumor growth and metastasis in ESCC. In this study, we aimed to study the effect of microRNA (miR)-21 on angiogenesis in ESCC and its underlying mechanism.Materials and MethodsInitially, the expression patterns of miR-21, SPRY1, and VEGF were determined in ESCC tissues and cells. The relationship between miR-21 and SPRY1 was identified using dual-luciferase reporter assay. Exosomes were subsequently isolated from the ESCC cells, followed by co-culture with the human umbilical venous endothelial cells (HUVECs). HUVEC proliferation and angiogenesis were determined by means of CCK-8, colony formation, and microtubule formation in vitro. Chicken chorioallantoic membrane (CAM) model and mouse xenograft model of ESCC cells were established to substantiate the function of miR-21 corresponding to the angiogenesis and tumor growth of ESCC, followed by microvascular density (MVD) evaluation.ResultsExpression patterns of miR-21 and VEGF were elevated, while the SPRY1 expression pattern was repressed in ESCC tissues and cells. The downregulation of miR-21 and exosome-derived miR-21 impeded the proliferation and angiogenesis in HUVECs. Our data revealed that miR-21 could negatively target SPRY1, and positively target VEGF. The downregulation of miR-21 could evidently encumber the angiogenesis and tumor growth of ESCC in vivo, as evidenced by the decrease in number of branches of the microvessels and MVD.ConclusionCollectively, ESCC cell-derived exosome containing miR-21 promotes the proliferation and angiogenesis of HUVECs via SPRY1 downregulation and VEGF upregulation.

Upregulation of miR-155 regulates group 2 innate lymphoid cells by targeting c-maf in allergic rhinitis

Group 2 innate lymphoid cells (ILC2s) and Th2 type immune response are critically involved in the pathogenesis of allergic rhinitis (AR), and this pathological process is influenced by microRNAs-mediated post-transcriptional regulation. The present study investigated the adaptation and function of miR-155 in AR patients and mouse model. We found that significantly increased miR-155 expression (1.63 ± 0.12 vs. 0.92 ± 0.11 in human, and 1.68 ± 0.15 vs. 1.06 ± 0.06 in mice) and ILC2s activity in nasal mucosa and serum in AR patients and mice. Administration of miR-155 antagomir significantly reduced the activity of ILC2s in nasal mucosa, suppressed the production of Th2 cytokines in serum and nasal mucosa, and alleviated the airway inflammation and allergic symptoms in AR mice, while miR-155 agomir increased ILC2s activity and production of Th2 cytokines and induced airway inflammation and allergic symptoms in control mice. Meanwhile, the expression of transcriptional factor c-Maf (0.57 ± 0.05 vs. 0.37 ± 0.04) in nasal mucosa in AR mice, which was significantly recovered by miR-155 antagomir (0.56 ± 0.04). Treatment with miR-155 agomir decreased c-Maf expression in nasal mucosa in control mice. This synchronized with the similar pattern in the current observations that miR-155 regulated Th2 cytokine (IL-4, IL-5, IL-9 and IL-13) production, airway inflammation and allergic symptoms in AR mice. Together, upregulation miR-155 suppressed the expression of transcriptional factor c-Maf and was critically involved in the ILC2s activation, which contributed to the airway inflammation and allergic symptoms in AR.

Regulation of MicroRNA-497-Targeting AKT2 Influences Tumor Growth and Chemoresistance to Cisplatin in Lung Cancer.

BackgroundMicroRNA-497 (miR-497) has been implicated in several cancers. Increasing studies demonstrate the role of AKT2 in cancers as an oncogene which is closely associated with tumor aggressiveness by enhancing cancer cell survival, migration and invasion However, miR-497/AKT2 axis in non-small cell lung cancer (NSCLC) remains unclear.MethodsQuantitative real-time PCR (qRT-PCR) was used to quantify the expression of miR-497 and its target gene. The function of miR-497 in lung cancer was investigated through in vitro and in vivo assays (cell proliferation assay, cell migration assay, colony formation assay, flow cytometry assay, immunoblotting and tumorigenesis assay). Luciferase reporter assay was conducted to confirm the target gene of miR-497.ResultsIn this study, we found that miR-497 was significantly downregulated in tumor tissues and blood samples of lung cancer patients. To understand the potential mechanism of miR-497 in inhibiting tumor growth, we showed that miR-497 blocked the activation of AKT2 and regulated cell proliferation, cell migration, colony formation and increases chemosensitivity of H1299 cells to cisplatin by inhibiting AKT2. MiR-497 also inhibited tumor growth and suppressed expression of AKT2 at the protein and mRNA levels in mouse xenograft tumors.ConclusionTaken together, our findings indicated that miR-497 suppresses the tumor growth by targeting AKT2, and the miR-497/AKT2 axis is a potential therapeutic target for NSCLC intervention.

Bacterial SOS Genes mucAB/umuDC Promote Mouse Tumors by Activating Oncogenes Nedd9/Aurkb via a miR-145 Sponge.

The mechanism of cancer induction involves an aberrant expression of oncogenes whose functions can be controlled by RNAi with miRNA. Even foreign bacterial RNA may interfere with the expression of oncogenes. Here we show that bacterial plasmid mucAB and its Escherichia coli genomic homolog umuDC, carrying homologies that match the mouse anti-miR-145, sequestered the miR-145 function in mouse BALB 3T3 cells in a tetracycline (Tet)-inducible manner, activated oncogene Nedd9 and its downstream Aurkb, and further enhanced microcolony formation and cellular transformation as well as the short fragments of the bacterial gene containing the anti-miR-145 sequence. Furthermore, mucAB transgenic mice showed a 1.7-fold elevated tumor incidence compared with wild-type mice after treatments with 3-methylcolanthrene. However, the mutation frequency in intestinal stem cells of the mucAB transgenic mice was unchanged after treatment with X-rays or ethyl-nitrosourea, indicating that the target of mucAB/umuDC is the promotion stage in carcinogenesis. IMPLICATIONS: Foreign bacterial genes can exert oncogenic activity via RNAi, if endogenously expressed. VISUAL OVERVIEW: http://mcr.aacrjournals.org/content/molcanres/18/9/1271/F1.large.jpg.

The impact of miR-9 in osteosarcoma: A study based on meta-analysis, TCGA data, and bioinformatics analysis.

The function of miR-9 in osteosarcoma is not well-investigated and controversial. Therefore, we conducted meta-analysis to explore the role of miR-9 in osteosarcoma, and collected relevant TCGA data to further testify the result. In addition, bioinformatics analysis was conducted to investigate the mechanism and related pathways of miR-9-3p in osteosarcoma.Literature search was operated on databases up to February 19, 2020, including PubMed, Web of Science, Science Direct, Cochrane Central Register of Controlled Trials, and Wiley Online Library, China National Knowledge Infrastructure, China Biology Medicine disc, Chongqing VIP, and Wan Fang Data. The relation of miR-9 expression with survival outcome was estimated by hazard ratio (HRs) and 95% CIs. Meta-analysis was conducted on the Stata 12.0 (Stata Corporation, TX). To further assess the function of miR-9 in osteosarcoma, relevant data from the TCGA database was collected. Three databases, miRDB, miRPathDB 2.0, and Targetscan 7.2, were used for prediction of target genes. Genes present in these 3 databases were considered as predicted target genes of miR-9-3p. Venny 2.1 were used for intersection analysis. Subsequently, GO, KEGG, and PPI network analysis were conducted based on the overlapping target genes of miR-9-3p to explore the possible molecular mechanism in osteosarcoma.Meta-analysis shown that overexpression of miR-9 was associated with worse overall survival (OS) (HR = 4.180, 95% CI: 2.880-6.066, P < .001, I = 23.5%). Based on TCGA data, osteosarcoma patients with overexpression of miR-9-3p (HR = 1.603, 95% CI: 1.028-2.499, P = .037) and miR-9-5p (HR = 1.698, 95% CI: 1.133-2.545, P = .01) also suffered poor OS. In bioinformatics analysis, 2 significant and important pathways were enriched: Wnt signaling pathway from gene ontology analysis (gene ontology:0016055, P-adjust = .008); hippo signaling pathway from Kyoto Encyclopedia of Genes and Genomes analysis (P-adjust = .007). Moreover, network analysis relevant protein-protein interaction was visualized, revealing 117 nodes and 161 edges.High miR-9 expression was associated with poor prognosis. Based on bioinformatics analysis, this study enhanced the understanding of the mechanism and related pathways of miR-9 in osteosarcoma.

MicroRNA-145 Inhibition Upregulates SIRT1 and Attenuates Autophagy in a Mouse Model of Lung Ischemia/Reperfusion Injury via NF-κB-dependent Beclin 1.

MicroRNA-145 (miR-145) has been shown to play a critical role in ischemia/reperfusion (I/R) injury; however, the expression and function of miR-145 in lung I/R injury have not been reported yet. This study aimed to elucidate the potential effects of miR-145 in lung I/R injury. Lung I/R mice models and hypoxia/reoxygenation (H/R) pulmonary microvascular endothelial cell models were established. The expression of miR-145 and sirtuin 1 (SIRT1) was measured with reverse transcription-quantitative polymerase chain reaction and Western blot analysis in mouse lung tissue and cells. Artificial modulation of miR-145 and SIRT1 (downregulation) was done in I/R mice and H/R cells. Additionally, Pao2/FiO2 ratio, wet weight-to-dry weight ratio, and cell apoptosis in mouse lung tissues were determined by blood gas analyzer, electronic balance, and deoxyuridine triphosphate-biotin nick end-labeling assay, respectively. Autophagy marker Beclin 1 and LC3 expression, NF-κB acetylation levels, and autophagy bodies were detected in cell H/R and mouse I/R models by Western blot analysis. pulmonary microvascular endothelial cell apoptosis was detected with flow cytometry. miR-145 was abundantly expressed in the lung tissue of mice and PMVECs following I/R injury. In addition, miR-145 directly targeted SIRT1, which led to significantly decreased Pao2/FiO2 ratio and increased wet weight-to-dry weight ratio, elevated acetylation levels and transcriptional activity of NF-κB, upregulated expressions of tumor necrosis factor-α, interleukins-6, and Beclin 1, autophagy bodies, cell apoptosis, as well as LC3-II/LC3I ratio. In summary, miR-145 enhances autophagy and aggravates lung I/R injury by promoting NF-κB transcriptional activity via SIRT1 expression.