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1.
Braz. j. biol ; 83: e242708, 2023. tab
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1339382

RESUMO

Abstract MicroRNAs (miRNAs) are essential nonprotein-coding genes. In a range of organisms, miRNAs has been reported to play an essential role in regulating gene expressions at post-transcriptional level. They participate in most of the stress responsive processes in plants. Drought is an ultimate abiotic stress that affects the crop production. Therefore understanding drought stress responses are essential to improve the production of agricultural crops. Throughout evolution, plants have developed their own defense systems to cope with the adversities of environmental stresses. Among defensive mechanisms include the regulations of gene expression by miRNAs. Drought stress regulates the expression of some of the functionally conserved miRNAs in different plants. The given properties of miRNAs provide an insight to genetic alterations and enhancing drought resistance in cereal crops. The current review gives a summary to regulatory mechanisms in plants as well as miRNAs response to drought stresses in cereal crops. Some possible approaches and guidelines for the exploitation of drought stress miRNA responses to improve cereal crops are also described.


Resumo MicroRNAs (miRNAs) são genes essenciais não codificadores de proteínas. Em uma variedade de organismos, foi relatado que miRNAs desempenham papel essencial na regulação da expressão gênica em nível pós-transcricional. Eles participam da maioria dos processos responsivos ao estresse nas plantas. A seca é um estresse abiótico final que afeta a produção agrícola. Portanto, compreender as respostas ao estresse da seca é essencial para melhorar a produção de safras agrícolas. Ao longo da evolução, as plantas desenvolveram seus próprios sistemas de defesa para lidar com as adversidades do estresse ambiental. Entre os mecanismos de defesa está a regulação da expressão gênica por miRNAs. O estresse hídrico regula a expressão de alguns dos miRNAs funcionalmente conservados em diferentes plantas. As propriedades dadas dos miRNAs fornecem uma visão das alterações genéticas e aumentam a resistência à seca nas safras de cereais. A revisão atual apresenta um resumo dos mecanismos regulatórios nas plantas, bem como a resposta dos miRNAs ao estresse hídrico nas plantações de cereais. Algumas abordagens e diretrizes possíveis para a exploração das respostas do miRNA ao estresse da seca para melhorar as safras de cereais também são descritas.


Assuntos
MicroRNAs/genética , Secas , Estresse Fisiológico/genética , Produtos Agrícolas/genética , Produção Agrícola
2.
J Mol Neurosci ; 72(3): 468-481, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34580818

RESUMO

Neuropathic pain (NP) involves metabolic processes that are regulated by metabolic genes and their non-coding regulator genes such as microRNAs (miRNAs). Here, we aimed at exploring the key miRNA signatures regulating metabolic genes involved in NP pathogenesis. We downloaded NP-related data from public databases and identified differentially expressed microRNAs (miRNAs) and mRNAs through differential gene expression analysis. The miRNA target prediction was performed, and integration with the differentially expressed metabolic genes (DEMGs) was used for constructing the miRNA-DEMG network. Subsequently, functional enrichment analysis and protein-protein interaction (PPI) analysis were performed to explore the role of DEMGs in the regulatory network. The drug prediction was performed based on the DEMGs in the miRNA-DEMG network. A total of 8251 differentially expressed mRNAs (4193 upregulated and 4058 downregulated), and 959 differentially expressed miRNAs (455 upregulated and 504 downregulated) were identified. Moreover, after target gene prediction, a miRNA-DEMG network composed of 22 miRNAs and 113 mRNAs was constructed. The network was constituted of 135 nodes and 236 edges. We found that DEMGs in the network were mainly enriched in metabolic pathways and metabolic processes. A total of 1200 drugs were predicted as potential therapeutics for NP based on the differentially expressed genes, while 170 drugs were predicted for the DEMGs in the miRNA-DEMG network. Conclusively, our study predicted drugs that may be effective against the metabolic changes induced by miRNA dysregulation in NP. This information will help further reveal the pathological mechanism of NP and provide more treatment options for NP patients.


Assuntos
MicroRNAs , Neuralgia , Biologia Computacional , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neuralgia/tratamento farmacológico , Neuralgia/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
3.
Int J Mol Med ; 49(4)2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35137921

RESUMO

The aim of the present study was to elucidate the effect of resveratrol on non­alcoholic steatohepatitis (NASH), and the molecular basis in mice and Hepa1­6 cells, in order to verify its therapeutic effect. C57BL/6J mice were fed a methionine­choline­deficient (MCD) diet to induce steatohepatitis and were treated with resveratrol. Mouse sera were collected for biochemical analysis and enzyme­linked immunosorbent assay, and livers were obtained for histological observation, and mmu­microRNA (miR)­599 and inflammation­related gene expression analysis. Hepa1­6 cells were treated with palmitic acid to establish a NASH cell model, and were then treated with resveratrol, or transfected with mmu­miR­599 mimic, mmu­miR­599 inhibitor or recombinant pregnane X receptor (PXR) plasmid. Subsequently, the cells were collected for mmu­miR­599 and inflammation­related gene expression analysis. Reverse transcription­quantitative polymerase chain reaction and western blotting were used to assess mmu­miR­599 expression levels, and the mRNA and protein expression levels of PXR and inflammation­related genes. The binding site of mmu­miR­599 in the PXR mRNA was verified by the luciferase activity assay. Mice fed an MCD diet for 4 weeks exhibited steatosis, focal necrosis and inflammatory infiltration in the liver. Resveratrol significantly reduced serum aminotransferase and malondialdehyde levels, and ameliorated hepatic injury. These effects were associated with reduced mmu­miR­599 expression, enhanced PXR expression, and downregulated levels of nuclear factor­κB, tumour necrosis factor­α, interleukin (IL)­1ß, IL­6, NOD­like receptor family pyrin domain­containing protein 3 and signal transducer and activator of transcription 3. Administration of the mmu­miR­599 mimic inhibited PXR expression in Hepa1­6 cells, whereas the mmu­miR­599 inhibitor exerted the opposite effect. A binding site for mmu­miR­599 was identified in the PXR mRNA sequence. Furthermore, overexpression of PXR inhibited the expression of inflammatory factors in Hepa1­6 cells. The present study provided evidence for the protective role of resveratrol in ameliorating steatohepatitis through regulating the mmu­miR­599/PXR pathway and the consequent suppression of related inflammatory factors. Resveratrol may serve as a potential candidate for steatohepatitis management.


Assuntos
MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Animais , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptor de Pregnano X/metabolismo , Resveratrol/farmacologia , Resveratrol/uso terapêutico
4.
Mol Cell Endocrinol ; 544: 111541, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-34973370

RESUMO

Glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH) accounts for a big portion of non-traumatic ONFH; nevertheless, the pathogenesis has not yet been fully understood. GC-induced endothelial dysfunction might be a major contributor to ONFH progression. The Gene Expression Omnibus (GEO) dataset was analyzed to identify deregulated miRNAs in ONFH; among deregulated miRNAs, the physiological functions of miR-122-5p on ONFH and endothelial dysfunction remain unclear. In the present study, miR-122-5p showed to be under-expressed within GC-induced ONFH femoral head tissues and GC-stimulated bone microvascular endothelial cells (BMECs). In human umbilical vein endothelial cells (HUVECs) and BMECs, GC stimulation significantly repressed cell viability, promoted cell apoptosis and increased the mRNA expression of proinflammatory cytokines, such as TNF-α, IL-1ß, and IFN-γ. After overexpressing miR-122-5p, GC-induced endothelial injuries were attenuated, as manifested by rescued cell viability, cell migration, and tube formation capacity. Regarding the BMP signaling, GC decreased the protein levels of BMP-2/6/7 and SMAD-1/5/8, whereas miR-122-5p overexpression significantly attenuated the inhibitory effects of GC on these proteins. Online tool and experimental analyses revealed the direct binding between miR-122-5p and GREM2, a specific antagonist of BMP-2. In contrast to miR-122-5p overexpression, GREM2 overexpression aggravated GC-induced endothelial injury; GREM2 silencing partially eliminated the effects of miR-122-5p inhibition on GC-stimulated HUVECs and BMECs. Finally, GREM2 silencing reversed the suppressive effects of GC on BMP-2/6/7 and SMAD-1/5/8, and attenuated the effects of miR-122-5p inhibition on these proteins upon GC stimulation. Conclusively, the present study demonstrates a miR-122-5p/GREM2 axis modulating the GC-induced endothelial damage via the BMP/SMAD signaling. Considering the critical role of endothelial function in ONFH pathogenesis, the in vivo role and clinical application of the miR-122-5p/GREM2 axis is worthy of further investigation.


Assuntos
Glucocorticoides , MicroRNAs , Apoptose , Citocinas/metabolismo , Cabeça do Fêmur/metabolismo , Cabeça do Fêmur/patologia , Glucocorticoides/metabolismo , Glucocorticoides/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Transdução de Sinais
5.
Clin. transl. oncol. (Print) ; 24(9): 1673-1681, septiembre 2022.
Artigo em Inglês | IBECS | ID: ibc-JHG-502

RESUMO

Colorectal cancer (CRC) is one of the most common cancers in the world. The incidence rate of cancer is high. The overall response to traditional treatment methods such as surgery, radiotherapy, and chemotherapy is not very satisfactory. Therefore, finding new therapeutic targets is very important for improving CRC treatment. In recent reports, the role of circRNAs in regulating colorectal angiogenesis has been gradually revealed. CircRNAs can indirectly act on angiogenesis pathways and regulate the expression of growth factors such as vascular endothelial growth factor (VEGF). CircRNAs are endogenous noncoding RNAs formed by pre-mRNAs through exon circular splicing. The covalent closed-loop structure makes these RNAs highly conserved and stable. CircRNAs have been found in human plasma, serum, urine, and other body fluids. Their highly conserved characteristics play important roles in many biological activities. CircRNAs can participate in the progression of many diseases by sponging miRNAs, interacting with proteins, and regulating transcription. Angiogenesis can provide nutrients and oxygen for tumour proliferation and metastasis. Angiogenesis is an important sign of the formation of the tumour microenvironment. Here, we will summarize the role of the latest circRNAs in the mechanism of angiogenesis in CRC and provide potential therapeutic targets for clinical treatment. (AU)


Assuntos
Humanos , Neoplasias Colorretais/patologia , MicroRNAs/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Splicing de RNA , Microambiente Tumoral
6.
Clin. transl. oncol. (Print) ; 24(9): 1715-1731, septiembre 2022.
Artigo em Inglês | IBECS | ID: ibc-JHG-505

RESUMO

Colorectal cancer (CRC) is the third most common malignant tumor worldwide and the fourth major cause of cancer-related death, with high morbidity and increased mortality year by year. Although significant progress has been made in the therapy strategies for CRC, the great difficulty in early diagnosis, feeble susceptibility to radiotherapy and chemotherapy, and high recurrence rates have reduced therapeutic efficacy resulting in poor prognosis. Therefore, it is urgent to understand the pathogenesis of CRC and unravel novel biomarkers to improve the early diagnosis, treatment and prediction of CRC recurrence. Long non-coding RNAs (lncRNAs) are non-coding RNAs with a length of more than 200 nucleotides, which are abnormally expressed in tumor tissues and cell lines, activating or inhibiting specific genes through multiple mechanisms including transcription and translation. A growing number of studies have shown that lncRNAs are important regulators of microRNAs (miRNAs, miRs) expression in CRC and may be promising biomarkers and potential therapeutic targets in the research field of CRC. This review mainly summarizes the potential application value of lncRNAs as novel biomarkers in CRC diagnosis, radiotherapy, chemotherapy and prognosis. Additionally, the significance of lncRNA SNHGs family and lncRNA–miRNA networks in regulating the occurrence and development of CRC is mentioned, aiming to provide some insights for understanding the pathogenesis of CRC and developing new diagnostic and therapeutic strategies. (AU)


Assuntos
Humanos , Biomarcadores Tumorais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , MicroRNAs/genética , Prognóstico
7.
Clin. transl. oncol. (Print) ; 24(9): 1764–1775, septiembre 2022.
Artigo em Inglês | IBECS | ID: ibc-JHG-509

RESUMO

PurposeTo explore the roles and underlying mechanisms of miR-1290 in determining the sensitivity of triple-negative breast cancer (TNBC) to radiation therapy.MethodsELISA was performed to detect the levels of IL-18 and IL-1β in radiosensitive cells and serum samples. The level of miR-1290 in radiosensitive cells and tissues was assessed by qRT–PCR assay. A luciferase reporter assay was performed to confirm NLRP3 as the target of miR-1290. Functionally, the roles of miR-1290 in TNBC radioresistance were analyzed by transfection of either miR-1290 mimic or miR-1290 inhibitor. Moreover, the involvement of the miR-1290/NLRP3 axis in TNBC radioresistance was analyzed by experiments with a miR-1290 mimic and NLRP3 overexpression. MTT and colony formation assays were used to detect radiation-induced cell viability and proliferation. qRT–PCR and western blot assays were used to detect pyroptosis markers (NLRP3, ACS and caspase-1).ResultsThe results showed that radioresistance in TNBC cells was associated with a reduction in pyroptosis. miR-1290 expression was increased in radioresistant cells, and it had higher expression levels in the radioresistant tumor tissues of TNBC patients compared to the radiosensitive samples. The miR-1290 mimic suppressed radiation-induced pyroptosis and reduced the radiosensitivity of TNBC cells. Moreover, we found that NLRP3 was a potential target of miR-1290. Overexpression of NLRP3 partly reversed the effects of miR-1290 on pyroptosis and radioresistance. The mouse models showed that miR-1290 suppressed tumor size, tumor weight and pyroptosis.ConclusionsmiR-1290/NLRP3-mediated pyroptosis may play an important role in determining radioresistance in TNBC and serve as a novel therapeutic option. (AU)


Assuntos
Humanos , Camundongos , MicroRNAs/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/radioterapia , Piroptose , Tolerância a Radiação/genética
8.
Front Endocrinol (Lausanne) ; 13: 934022, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909518

RESUMO

Diabetic nephropathy (DN) is one of the common chronic complications of diabetes with unclear molecular mechanisms, which is associated with end-stage renal disease (ESRD) and chronic kidney disease (CKD). Our study intended to construct a competing endogenous RNA (ceRNA) network via bioinformatics analysis to determine the potential molecular mechanisms of DN pathogenesis. The microarray datasets (GSE30122 and GSE30529) were downloaded from the Gene Expression Omnibus database to find differentially expressed genes (DEGs). GSE51674 and GSE155188 datasets were used to identified the differentially expressed microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), respectively. The DEGs between normal and DN renal tissues were performed using the Linear Models for Microarray (limma) package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to reveal the mechanisms of DEGs in the progression of DN. The protein-protein interactions (PPI) of DEGs were carried out by STRING database. The lncRNA-miRNA-messenger RNA (mRNA) ceRNA network was constructed and visualized via Cytoscape on the basis of the interaction generated through the miRDB and TargetScan databases. A total of 94 significantly upregulated and 14 downregulated mRNAs, 31 upregulated and 121 downregulated miRNAs, and nine upregulated and 81 downregulated lncRNAs were identified. GO and KEGG pathways enriched in several functions and expression pathways, such as inflammatory response, immune response, identical protein binding, nuclear factor kappa b (NF-κB) signaling pathway, and PI3K-Akt signaling pathway. Based on the analysis of the ceRNA network, five differentially expressed lncRNAs (DElncRNAs) (SNHG6, KCNMB2-AS1, LINC00520, DANCR, and PCAT6), five DEmiRNAs (miR-130b-5p, miR-326, miR-374a-3p, miR-577, and miR-944), and five DEmRNAs (PTPRC, CD53, IRF8, IL10RA, and LAPTM5) were demonstrated to be related to the pathogenesis of DN. The hub genes were validated by using receiver operating characteristic curve (ROC) and real-time PCR (RT-PCR). Our research identified hub genes related to the potential mechanism of DN and provided new lncRNA-miRNA-mRNA ceRNA network that contributed to diagnostic and potential therapeutic targets for DN.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , MicroRNAs , RNA Longo não Codificante , Biomarcadores , Biologia Computacional , Nefropatias Diabéticas/genética , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética
9.
Front Endocrinol (Lausanne) ; 13: 836152, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909542

RESUMO

Background: Diabetic foot ulcer (DFU) is a severe complication characterized by low-grade infectious inflammation and probably associated with specific competitive endogenous RNAs (ceRNAs) and infiltrating immune cells. Nonetheless, no reliable biomarkers are used for detecting infectious inflammation in DFU. Therefore, it is essential to explore potential biomarkers for the accurate diagnosis and treatment of DFU. Methods: The gene expression profile was retrieved from Gene Expression Omnibus (GEO) database and divided into two groups, namely, standard samples and DFU samples. To establish the ceRNA networks, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were utilized to analyze differential expression genes (DEGs). The cell type identification was achieved by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm to screen-specific immune-infiltrating cells associated with DFU. Results: A ceRNA network was constructed with 20 differential expression circRNA (DEcircRNAs), 11 differential expression microRNAs (DEmiRNAs), and 9 differential expression mRNAs (DEmRNAs). Functional enrichment analysis demonstrated that DFU was mainly enriched in vascular endothelial growth factor (VEGF) and T-cell receptor signaling. In addition, CIBERSORT estimation indicated that CD8+ T cells and Monocytes were significantly related to the expression of IL-6, a DFU-specific infectious inflammation factor. Conclusion: This study identified that some significant ceRNAs (JUNB, GATA3, hsa-circ-0049271 and hsa-circ-0074559) and infiltrating immune cells (CD8+ T cells and monocytes) might be related to DFU infectious inflammation.


Assuntos
Diabetes Mellitus , Pé Diabético , MicroRNAs , Biomarcadores , Linfócitos T CD8-Positivos , Pé Diabético/genética , Humanos , Inflamação/genética , MicroRNAs/genética , Fator A de Crescimento do Endotélio Vascular
10.
Front Endocrinol (Lausanne) ; 13: 891313, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35909545

RESUMO

Osteoporosis is a bone metabolic disorder characterized by decreased bone density and deteriorated microstructure, which increases the risk of fractures. The imbalance between bone formation and bone resorption results in the occurrence and progression of osteoporosis. Osteoblast-mediated bone formation, osteoclast-mediated bone resorption and macrophage-regulated inflammatory response play a central role in the process of bone remodeling, which together maintain the balance of the osteoblast-osteoclast-macrophage (OB-OC-MΦ) axis under physiological conditions. Bone formation and bone resorption disorders caused by the imbalance of OB-OC-MΦ axis contribute to osteoporosis. Many microRNAs are involved in the regulation of OB-OC-MΦ axis homeostasis, with microRNA-23a (miR-23a) being particularly crucial. MiR-23a is highly expressed in the pathological process of osteoporosis, which eventually leads to the occurrence and further progression of osteoporosis by inhibiting osteogenesis, promoting bone resorption and inflammatory polarization of macrophages. This review focuses on the role and mechanism of miR-23a in regulating the OB-OC-MΦ axis to provide new clinical strategies for the prevention and treatment of osteoporosis.


Assuntos
Reabsorção Óssea , MicroRNAs , Osteoporose , Reabsorção Óssea/genética , Reabsorção Óssea/metabolismo , Humanos , Macrófagos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoblastos/metabolismo , Osteoclastos/metabolismo , Osteoporose/etiologia , Osteoporose/genética , Osteoporose/fisiopatologia , Osteoporose/terapia
11.
Comput Math Methods Med ; 2022: 9304392, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912140

RESUMO

Objective: Long noncoding RNA neuroblastoma-associated transcript 1 (NBAT1) is implicated in the progression of various cancers. Nevertheless, its biological function in endometrial cancer (EC) remains unknown. Methods: The levels of NBAT1, miR-21-5p, and PTEN in EC cells and EC tissues were examined by RT-qPCR. Western blot was carried out to assess the protein expression of PTEN. The dual-luciferase reporter assay was conducted to explore the interactions among NBAT1, miR-21-5p, and PTEN. The effect of NBAT1 on EC proliferation, metastasis, and apoptosis was evaluated by CCK-8, transwell assays, wound healing, and flow cytometry. miR-21-5p mimics or NBAT1+miR-21-5p were transfected into HEC-1A and Ishikawa cells to investigate whether NBAT1 regulated EC tumorigenesis via sponging miR-21-5p. Results: NBAT1 is downregulated, and miR-21-5p is upregulated in EC cells and tumor tissues. Overexpression of NBAT1 inhibits the proliferation, migration, and invasion abilities of EC cells and facilitated apoptosis. NBAT1 directly binds and negatively regulates miR-21-5p in EC. miR-21-5p mimics reverses the effect of lncRNA NBAT1 overexpression on the proliferation and migration of EC cells. PTEN is a downstream gene of miR-21-5p. lncRNA NBTA1 elevates PTEN expression via sponging miR-21-5p. Conclusions: lncRNA NBAT1 acts as a tumor suppressor in EC via regulating PTEN through sponging miR-21-5p.


Assuntos
Neoplasias do Endométrio , MicroRNAs , Neuroblastoma , RNA Longo não Codificante , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias do Endométrio/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
12.
Comput Math Methods Med ; 2022: 9088727, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912153

RESUMO

Objective: Acute inflammation and oxidative stress are present in large numbers in patients with acute lung injury (ALI). This investigation probed miR-135a-5p/TBK1 axis within ALI together with its new therapeutic target. Methods: MLE-12 cultures were treated with lipopolysaccharide (LPS) and transfected with miR-135a-5p mimics or TBK1 vector. An ALI mouse model was also established. Analysis was done on the relationships between TBK1 and miR-135a-5p. Inflammatory components, SOD, MDA, and ROS content were all assessed. Results: Obvious inflammatory lesions were observed in lung tissues of ALI mice. Overexpression of miR-135a-5p or TBK1 knockdown remarkably decreased IL-1ß, IL-6, and TNF-α serum concentrations and increased IL-10 level within lung tissues. Activated NRF2/TXNIP pathway and oxidative stress were additionally found within ALI murines, which were regulated by miR-315a-5p and TBK1. Further research revealed that miR-135a-5p negatively regulated TBK1 expression to mediate proinflammatory response and oxidative stress. Conclusion: miR-135a-5p targeted TBK1 to regulate inflammatory/oxidative stress responses in ALI. Such results might bring a new potential target for ALI treatment.


Assuntos
Lesão Pulmonar Aguda , MicroRNAs , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , Animais , Antioxidantes , Proteínas de Transporte , Lipopolissacarídeos , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Fator 2 Relacionado a NF-E2/genética , Proteínas Serina-Treonina Quinases/genética , Tiorredoxinas/metabolismo
13.
Comput Math Methods Med ; 2022: 6058720, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35912155

RESUMO

Lung cancer has a higher incidence and mortality rate than other cancers, and over 80% of lung cancer cases were classified as non-small-cell lung cancer (NSCLC). TRIM66 is one of the crucial members of TRIM, which has a deep connection with the behavior of various malignant tumors. But it remains uncertain regarding its exact function and underlying mechanism in NSCLC. In our study, qRT-PCR and Western blot were employed to validate that TRIM66 was overexpressed in NSCLC. The migration, invasion, and epithelial-mesenchymal transformation (EMT) progression of NSCLC cells were determined by Western blotting and Transwell experiments after knocking down TRIM66, and it was found that knockdown TRIM66 inhibited the migration, invasion, and EMT processes of NSCLC cells. Next, the binding relationship between TRIM66 and MMP9 was verified by Co-IP assay. After determining the interaction between them, rescue assays showed that overexpression of MMP9 was capable to promote the migration, invasion, and EMT of NSCLC cells. However, the transfection of si-TRIM66 could reverse this facilitating effectiveness. To sum up, we concluded that by targeting MMP9, TRIM66 could exert a cancer-promoting role in the progression of NSCLC cells.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Pulmonares/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , MicroRNAs/metabolismo , Invasividade Neoplásica/genética
14.
Eur Rev Med Pharmacol Sci ; 26(14): 5285-5296, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35916829

RESUMO

OBJECTIVE: Acute respiratory distress syndrome (ARDS) is an inflammatory lung disease that has a high rate of morbidity and mortality. It's an acute diffusive lung injury caused by the release of pro-inflammatory cytokines into the lungs. Specific microRNAs have been identified to play a crucial role in the renin-angiotensin system signaling pathways the main pathophysiological pathway responsible for ARDS. Since the ARDS life-threatening complication associated with COVID-19 is an ongoing challenge, this current study aimed to investigate the potential efficacy of xanthenone in the treatment of ARDS induced with LPS in mice through ACE2 activation and modulation of miR-200 and ACE2/Ang 1-7 pathways. MATERIALS AND METHODS: Mice were categorized into three groups randomly. The first set of mice served as the normal control group. The ARDS group was injected with LPS (15 mg/kg; i.p.). The last group was treated with xanthenone (2 mg/kg/day; p.o.) for one week before the LPS injection. RESULTS: Xanthenone treatment resulted in a significant down-regulation of miRNA-200 expression, leading to the activation of ACE2 accompanied with marked inhibition of Angiotensin II as well as increases the levels of Ang 1-7 and SP-A. CONCLUSIONS: Xanthenone has the potential to be a promising therapeutic drug for the treatment of ARDS COVID-19 complication through activation of ACE2/Ang 1-7 pathways. Graphical Abstract: https://www.europeanreview.org/wp/wp-content/uploads/Graphical_abstract.tif.


Assuntos
Lesão Pulmonar Aguda , COVID-19 , MicroRNAs , Síndrome do Desconforto Respiratório , Lesão Pulmonar Aguda/metabolismo , Enzima de Conversão de Angiotensina 2 , Animais , COVID-19/tratamento farmacológico , Lipopolissacarídeos/efeitos adversos , Camundongos , Peptidil Dipeptidase A/metabolismo , Síndrome do Desconforto Respiratório/tratamento farmacológico , Transdução de Sinais
15.
Mol Med Rep ; 26(4)2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35920180

RESUMO

Chronic thromboembolic pulmonary hypertension (CTEPH) is a leading cause of pulmonary hypertension. The present study investigated the mechanisms of long non­coding RNA growth arrest­specific transcript 5 (GAS5) on spermidine (SP)­induced autophagy. Pulmonary artery endothelial cells (PAECs) were collected from patients with CTEPH and the rat model. Immunofluorescence, Western blots, reverse transcription­quantitative polymerase chain reaction, bioinformatics, rapid amplification of cDNA ends assays, luciferase reporter assays, RNA­binding protein immunoprecipitation assays, GFP­LC3 adenoviruses, tfLC3 assays and transmission electron microscopy were performed. The results revealed that SP­induced autophagy increased GAS5 in PAECs. The upregulation of GAS5 enhanced and the downregulation of GAS5 reversed the roles of SP in PAECs. Furthermore, GAS5 promoted SP­induced autophagy in PAECs by targeting miRNA­31­5p. The miRNA­31­5p mimic suppressed and the inhibitor promoted SP­induced autophagy. Furthermore, N­Acetyltransferase 8 Like (NAT8L) was a target gene of miRNA­31­5p and knockdown of NAT8L inhibited the autophagic levels of PAECs. In vivo, SP treatment decreased miRNA­31­5p and increased NAT8L levels, which was reversed by the knockdown of GAS5. The downregulation of GAS5 abolished the stimulatory role of SP in PAECs of CTEPH rats. In conclusion, GAS5 promoted SP­induced autophagy through miRNA­31­5p/NAT8L signaling pathways in vitro and in vivo and GAS5 may be a promising molecular marker for therapies of CTEPH.1.


Assuntos
Hipertensão Pulmonar , MicroRNAs , RNA Longo não Codificante , Acetiltransferases/genética , Animais , Autofagia , Células Endoteliais/metabolismo , MicroRNAs/metabolismo , Artéria Pulmonar/metabolismo , RNA Longo não Codificante/metabolismo , Ratos , Espermidina
16.
Int J Oncol ; 61(3)2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35920182

RESUMO

Advanced gallbladder cancer (GBC) is one of the most malignant of all types of biliary tract cancers that is associated with poor prognosis and high mortality. Accumulating evidence suggest that the B7 family of proteins serve an essential role in various types of cancers, including GBC. However, the potential function and regulatory mechanism of human endogenous retrovirus­H long terminal repeat­associating protein 2 (HHLA2; also known as B7­H7 or B7H5) in GBC remain poorly understood. In the present study, immunohistochemistry was used to examine the expression pattern of HHLA2 in samples from 89 patients with GBC. The possible association between HHLA2 expression and the clinicopathological parameters, including prognosis, were then assessed. Using lentiviruses, overexpression of HHLA2 plasmid or short­hairpin RNA (shRNA) of HHLA2 were transfected into GBC­SD cells to overexpress or knock down HHLA2 expression, respectively. The effects of HHLA2 overexpression and knockdown on the epithelial­mesenchymal transition (EMT) process on GBC­SD cells were measured by the western blotting and immunofluorescence staining of collagen I, N­cadherin, E­cadherin, vimentin and α­SMA. By contrast, changes in cell proliferation were measured using EdU assay. Cell invasion and migration were assessed using Transwell and wound­healing assays, respectively. In addition, a xenograft mouse model was established to evaluate the tumorigenic ability of the GBC cell line in vivo after stable transfection with lentivirus for HHLA2 overexpression or shRNA for HHLA2 knockdown. The regulatory relationships among TGF­ß1, long non­coding RNA (lncRNA) H19 (H19) and HHLA2 were then investigated. The mRNA expression of lncRNA H19 were assessed using reverse transcription­quantitative PCR, whereas the expression levels of HHLA2 were detected by western blotting and immunofluorescence staining. HHLA2 expression was found to gradually increase as the stages of the GBC samples become more advanced. In addition, the expression level of HHLA2 was calculated to be positively associated with the Nevin stage, American Joint Committee on Cancer stage, tumor invasion and regional lymph node metastasis but was negatively associated with the overall patient survival (OS). In vitro experiments demonstrated that overexpression of HHLA2 promoted GBC migration, invasion, proliferation and EMT, whereas in vivo experiments found a promoting role of HHLA2 overexpression on GBC tumor growth. After transfection with lentiviruses encoding the overexpression plasmid of lncRNA H19, GBC migration, invasion, proliferation and EMT were increased. By contrast, knocking down HHLA2 expression suppressed TGF­ß1­ or lncRNA H19 overexpression­induced GBC migration, invasion, proliferation and EMT. In addition, HHLA2 knockdown significantly reduced the sizes of the GBC tumors in vivo. These results suggest that HHLA2 overexpression can promote GBC progression. Conversely, ablation of HHLA2 expression inhibited both TGF­ß1­ and lncRNA H19­induced GBC progression, suggesting that HHLA2 is a potential therapeutic target for this disease.


Assuntos
Neoplasias da Vesícula Biliar , MicroRNAs , RNA Longo não Codificante , Animais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Imunoglobulinas/genética , Imunoglobulinas/metabolismo , Camundongos , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno , Fator de Crescimento Transformador beta1/genética
17.
Sci Rep ; 12(1): 13503, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931808

RESUMO

Clear cell renal cell carcinoma (ccRCC) is the most common renal cancer. Identification of ccRCC likely to progress, despite an apparent low risk at the time of surgery, represents a key clinical issue. From a cohort of adult ccRCC patients (n = 443), we selected low-risk tumors progressing within a 5-years average follow-up (progressors: P, n = 8) and non-progressing (NP) tumors (n = 16). Transcriptome sequencing, miRNA sequencing and proteomics were performed on tissues obtained at surgery. We identified 151 proteins, 1167 mRNAs and 63 miRNAs differentially expressed in P compared to NP low-risk tumors. Pathway analysis demonstrated overrepresentation of proteins related to "LXR/RXR and FXR/RXR Activation", "Acute Phase Response Signaling" in NP compared to P samples. Integrating mRNA, miRNA and proteomic data, we developed a 10-component classifier including two proteins, three genes and five miRNAs, effectively differentiating P and NP ccRCC and capturing underlying biological differences, potentially useful to identify "low-risk" patients requiring closer surveillance and treatment adjustments. Key results were validated by immunohistochemistry, qPCR and data from publicly available databases. Our work suggests that LXR, FXR and macrophage activation pathways could be critically involved in the inhibition of the progression of low-risk ccRCC. Furthermore, a 10-component classifier could support an early identification of apparently low-risk ccRCC patients.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , Adulto , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/patologia , Progressão da Doença , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Renais/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Proteômica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
18.
BMC Cancer ; 22(1): 857, 2022 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35931993

RESUMO

BACKGROUND: Liver cirrhosis is a well-known risk factor for hepatocellular carcinoma (HCC). However, some HCC cases can also originate from non-cirrhotic livers. The aim of this study was to identify key circular RNAs (circRNAs) associated with the tumorigenesis of non-cirrhotic liver disease. METHODS: The differently expressed circRNAs between non-cirrhotic and cirrhotic HCCs were assessed with use of high-throughput circRNAs sequencing and validated with quantitative reverse transcription polymerase chain reaction (qRT-PCR). Potential biological functions of these dysregulated circRNAs were predicted with use of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A circRNA-miRNA-mRNA regulation network was constructed as achieved with use of miRanda software and visualized using Cytoscape software. Biological functions of the four most prominent dysregulated circRNAs identified were confirmed by in vitro experiments. Moreover, possible translations of these dysregulated circRNAs were also predicted. RESULTS: A total of 393 dysregulated circRNAs were identified between non-cirrhotic and cirrhotic HCC, including 213 that were significantly up-regulated and 180 significantly down-regulated circRNAs. Expression levels of the six most prominent dysregulated circRNAs were further validated using qRT-PCR. Many tumor related miRNAs were involved in the circRNA-miRNA-mRNA networks, including miR-182-5p, miR-561-3p, miR-125a-5p, miR-145, miR-23b-3p and miR-30e-3p, and downstream mRNAs of dysregulated circRNAs were significantly related with biological processes involved in the progression of tumors, including proliferation, migration, differentiation, and focal adhesion. Results from the in vitro experiments demonstrated that the most prominent dysregulated circRNAs exerted notable effects upon the proliferation and migration of HCC cells. Finally, we also identified 19 dysregulated circRNAs having potential for the coding of functional peptides. CONCLUSION: The results of this present study indicate that circRNAs may play important roles in tumorigenesis of non-cirrhotic HCC. Such findings provide some novel insights and pave the way for the development of future studies directed at investigating the initiation and treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Carcinogênese , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA/genética , RNA/metabolismo , RNA Circular/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Análise de Sequência de RNA
19.
J Mol Diagn ; 24(8): 867-877, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35934321

RESUMO

Detection of serum embryonic miRNAs miR-371a-3p and miR-372-3p has been proposed to aid in diagnosis, prognosis, and management of patients with testicular germ cell tumors (GCTs). This study describes the analytical validation and performance of a laboratory-developed test to detect these miRNA targets by stem loop real-time quantitative RT-PCR (RT-qPCR) in serum from patients with GCTs. The assay was standardized using an exogenous spike-in control of nonhuman miRNA from Caenorhabditis elegans (cel-miR-39-3p) to assess extraction efficiency, and an endogenous housekeeping miRNA, miR-30b-5p, to control for miRNA normalization. miRNA results were expressed as relative expression level, using the comparative threshold cycle method (2ΔΔCT). Analytical sensitivity of miR-371a-3p and miR-372-3p was 12.5 and 1.25 copies/µL, respectively. Clinical accuracy was evaluated using GCT patients with (n = 34) and without (n = 17) active disease. Positive/negative cutoffs and indeterminate findings were established on the basis of results from healthy volunteers (n = 25) and assay precision. miR-371a-3p and miR-372-3p exhibited a sensitivity of 81.8% and 87.5%, respectively, and a specificity of 100% and 94%, respectively, and an area under the receiver operating characteristic curve of 0.93 and 0.95, respectively. Taken together, RT-qPCR testing for serum miR-371a-3p and miR-372-3p represents a robust, sensitive, and specific clinical assay to aid in the clinical management of patients with GCT.


Assuntos
MicroRNAs , Neoplasias Embrionárias de Células Germinativas , Biomarcadores Tumorais/genética , Humanos , Laboratórios Clínicos , Masculino , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Testiculares
20.
Anal Chim Acta ; 1221: 340132, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35934367

RESUMO

MicroRNAs (miRNAs) and p53 gene can serve as valuable biomarkers for the diagnosis of a variety of cancers. Nevertheless, although the development of the DNA nanostructure on the detection of cancer-related biomarkers was initially demonstrated several years ago, the challenges of developing simpler, cheaper, and multi-level detection DNA biosensors persist. Herein, based on the rolling circle amplification (RCA) coupled with the target-triggered skill, we have developed a well-designed detecting platform. In this study, the dumbbell-shaped probes (DPP) could be cyclized and initiated through targets, thus beginning the target-catalyst RCA (tc-RCA) reaction, therefore engendering numerous dumbbell probe amplicons (DPA). Thereafter the probe primers (PP) mutually complementary to the loop of DPA was introduced, leading to the branch strand displacement reaction (B-SDA). SYBR Green I can effectively bind to the amplified double-stranded structures as a fluorescent reporter. Altering the target-binding sequence of the DPP, this biosensor can also be applied to detect different biomarkers. As a consequence, target miR-21 and p53 gene can be detected down to 0.65 fM and 2.04 fM respectively with a wide dynamic range. Moreover, we have also achieved the qualitative detection of interesting targets in cell lysates as well as the complex biological substrates and compared the results with reverse transcription quantitative PCR (RT-qPCR), thereby indicating the potential application in clinical diagnosis and biomedical research.


Assuntos
MicroRNAs , Técnicas de Amplificação de Ácido Nucleico , Biomarcadores , DNA/química , Genes p53 , Limite de Detecção , MicroRNAs/análise , MicroRNAs/genética , Técnicas de Amplificação de Ácido Nucleico/métodos
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