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1.
Clin Exp Rheumatol ; 37 Suppl 120(5): 40-47, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31621575

RESUMO

MicroRNAs are small double-stranded RNAs, which negatively regulate gene expression and have been shown to have key roles in both chondrocyte development and cartilage homeostasis with age. Deletion of all microRNAs in chondrocytes leads to skeletal growth defects in mice, whilst deletion of specific microRNAs, e.g. miR-140, leads to premature articular cartilage degradation and increased susceptibility to posttraumatic osteoarthritis. Studies comparing microRNA expression in normal human articular cartilage compared to osteoarthritic cartilage show differential expression, but varying sample groups make interpretation difficult. MicroRNAs have been proposed as circulating biomarkers of osteoarthritis, but again, this differs amongst patient cohorts. Many micro-RNAs have been shown to have roles in chondrocyte phenotype via signalling pathways, apoptosis, autophagy and senescence. Modulating microRNAs in the joint has been shown to reduce osteoarthritis in animal models and translating this to man as a novel therapeutic strategy will be key.


Assuntos
Autofagia , Cartilagem Articular , MicroRNAs , Osteoartrite , Animais , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Condrócitos/metabolismo , Condrócitos/patologia , Humanos , Masculino , Camundongos , MicroRNAs/genética , MicroRNAs/fisiologia , Osteoartrite/genética , Osteoartrite/metabolismo
2.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 54(10): 662-669, 2019 Oct 09.
Artigo em Chinês | MEDLINE | ID: mdl-31607001

RESUMO

Objective: To investigate the effect of microRNA-26a-5p on osteogenic differentiation of human periodontal ligament stem cells (hPDLSC) and its related mechanisms. Methods: hPDLSC in periodontal tissues from healthy adults and hPDLSC from periodontitis patients (PPDLSC) were isolated and cultured in vitro, respectively. The PPDLSC were divided into Ⅰ, Ⅱ, Ⅲ, Ⅳ and Ⅴ groups. Group Ⅰ is control group, and the other four groups were transiently transfected with miR-NC, miR-26a-5p, antimiR-NC and antimiR-26a-5p lentiviral vectors, respectively. The osteogenic differentiation abilities of the cells in vitro were determined by alizarin red staining, alkaline phosphatase (ALP) activity assay and real-time quantitative PCR (qPCR). Totally 40 male mice (6-weeks) were equally divided into five groups with 8 mice in each group. The PPDLSCs cells (1×10(7)/ml) in Ⅰ, Ⅱ, Ⅲ, Ⅳ and Ⅴ groups, which adhered to hydroxyapatine-tricalcium phosphate (HA-TCP), were implanted into the nude mice subcutaneously and the animal models were constructed to analyze the effect of miR-26a-5p on the osteogenic differentiation of PPDLSCs in vivo. PPDLSCs were divided into A, B, C, D groups, and transfected with miR-26a-5p+Wnt5a-Wt, miR-NC+Wnt5a-Wt, miR-26a-5p+Wnt5a-Mut and miR-NC+Wnt5a-Mut in each of the above mentioned 5 groups, respectively. The luciferase activity assay was used to detect the relative luciferase in A, B, C and D groups to analyze the targeting relationship between miR-26a-5p and Wnt5a. Osteogenic differentiation related proteins expression were analyzed by western blotting. Results: hPDLSC and PPDLSC were observed consistent with the characteristics of mesenchymal stem cells and had osteogenic differentiation ability in vitro. Compared with hPDLSC [(89.87±8.12)%], the osteogenic capacity of PPDLSC [(31.46±6.56)%] was significantly lower (P<0.05). The ALP activity (1.88±0.59), calcified nodules (79.88±5.92), the expression of the osteogenic differentiation markers Runt-related transcription factor 2 (Runx2) (2.40±0.70), ALP (2.10±0.60) and osteocalcin (3.00±0.90) mRNA in the PPDLSC from Group Ⅲ were significantly higher in comparison with the control group [(0.88±0.34), (29.69±2.65), (1.30±0.30), (0.09±0.25), (1.71±0.50)], while those from Group Ⅴ[(0.44±0.07), (14.83±3.05), (0.50±0.11), (0.30±0.08) and (0.80±0.17)] were significantly lower (P<0.05). In vivo studies in nude mice showed that the proportion of the osteogenic region [(34.96±5.65)%] in the miR-26a-5p group was significantly increased in comparison with the control group [(23.28±3.03)%], while in the antimiR-26a-5p group [(8.02±2.27)%] was significantly lower (P<0.05). The luciferase activity of the Group A (0.46±0.06) was significantly lower than Group B (3.46±0.45) (P<0.05). Compared with the control group, the expression levels of Wnt5a protein, calmodulin kinase Ⅱ and protein kinase C proteins in the Group Ⅲ were significantly decreased, while those in the GroupⅤ were significantly increased (P<0.05). Conclusions: MicroRNA-26a-5p could promote osteogenic differentiation of PPDLSC in vivo and in vitro, and its mechanism might be inhibiting the activation of Wnt/Ca(2+) signaling pathway by targeting Wnt5a.


Assuntos
MicroRNAs , Osteogênese , Ligamento Periodontal , Proteína Wnt-5a , Adulto , Animais , Diferenciação Celular , Humanos , Masculino , Camundongos , Camundongos Nus , MicroRNAs/fisiologia , Ligamento Periodontal/metabolismo , Células-Tronco , Proteína Wnt-5a/metabolismo
4.
BMC Plant Biol ; 19(1): 370, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31438851

RESUMO

BACKGROUND: Accumulating evidences show that SPLs are crucial regulators of plant abiotic stress tolerance and the highly conserved module miR156/SPL appears to balance plant growth and stress responses. The halophyte Tamarix chinensis is highly resistant to salt tress. SPLs of T. chinensis (TcSPLs) and theirs roles in salt stress responses remain elusive. RESULTS: In this study, we conducted a systematic analysis of the TcSPLs gene family including 12 members belonging to 7 groups. The physicochemical properties and conserved motifs showed divergence among groups and similarity in each group. The microRNA response elements (MREs) are conserved in location and sequence, with the exception of first MRE within TcSPL5. The miR156-targeted SPLs are identified by dual-luciferase reporter assay of MRE-miR156 interaction. The digital expression gene profiles cluster suggested potential different functions of miR156-targeted SPLs vs non-targeted SPLs in response to salt stress. The expression patterns analysis of miR156-targeted SPLs with a reverse expression trend to TcmiR156 suggested 1 h (salt stress time) could be a critical time point of post-transcription regulation in salt stress responses. CONCLUSIONS: Our work demonstrated the post-transcription regulation of miR156-targeted TcSPLs and transcription regulation of non-targeted TcSPLs in salt stress responses, and would be helpful to expound the miR156/SPL-mediated molecular mechanisms underlying T. chinensis salt stress tolerance.


Assuntos
MicroRNAs/fisiologia , Proteínas de Plantas/fisiologia , RNA de Plantas/fisiologia , Estresse Salino/genética , Tamaricaceae/genética , Fatores de Transcrição/fisiologia , Motivos de Aminoácidos , Sequência Conservada , Genes de Plantas , Família Multigênica , Filogenia , Transcriptoma
5.
BMC Plant Biol ; 19(1): 336, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31370790

RESUMO

BACKGROUND: APETALA2-like genes encode plant-specific transcription factors, some of which possess one microRNA172 (miR172) binding site. The miR172 and its target euAP2 genes are involved in the process of phase transformation and flower organ development in many plants. However, the roles of miR172 and its target AP2 genes remain largely unknown in Brassica napus (B. napus). RESULTS: In this study, 19 euAP2 and four miR172 genes were identified in the B. napus genome. A sequence analysis suggested that 17 euAP2 genes were targeted by Bna-miR172 in the 3' coding region. EuAP2s were classified into five major groups in B.napus. This classification was consistent with the exon-intron structure and motif organization. An analysis of the nonsynonymous and synonymous substitution rates revealed that the euAP2 genes had gone through purifying selection. Whole genome duplication (WGD) or segmental duplication events played a major role in the expansion of the euAP2 gene family. A cis-regulatory element (CRE) analysis suggested that the euAP2s were involved in the response to light, hormones, stress, and developmental processes including circadian control, endosperm and meristem expression. Expression analysis of the miR172-targeted euAP2s in nine different tissues showed diverse spatiotemporal expression patterns. Most euAP2 genes were highly expressed in the floral organs, suggesting their specific functions in flower development. BnaAP2-1, BnaAP2-5 and BnaTOE1-2 had higher expression levels in late-flowering material than early-flowering material based on RNA-seq and qRT-PCR, indicating that they may act as floral suppressors. CONCLUSIONS: Overall, analyses of the evolution, structure, tissue specificity and expression of the euAP2 genes were peformed in B.napus. Based on the RNA-seq and experimental data, euAP2 may be involved in flower development. Three euAP2 genes (BnaAP2-1, BnaAP2-5 and BnaTOE1-2) might be regarded as floral suppressors. The results of this study provide insights for further functional characterization of the miR172 /euAP2 module in B.napus.


Assuntos
Brassica napus/genética , Flores/crescimento & desenvolvimento , Genes de Plantas/genética , MicroRNAs/genética , Brassica napus/crescimento & desenvolvimento , Mapeamento Cromossômico , Sequência Conservada/genética , Genes de Plantas/fisiologia , Estudo de Associação Genômica Ampla , MicroRNAs/fisiologia , Filogenia , Alinhamento de Sequência
6.
Gut ; 68(11): 2065-2079, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31300518

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is associated with a thorough reprogramming of hepatic metabolism. Epigenetic mechanisms, in particular those associated with deregulation of the expressions and activities of microRNAs (miRNAs), play a major role in metabolic disorders associated with NAFLD and their progression towards more severe stages of the disease. In this review, we discuss the recent progress addressing the role of the many facets of complex miRNA regulatory networks in the development and progression of NAFLD. The basic concepts and mechanisms of miRNA-mediated gene regulation as well as the various setbacks encountered in basic and translational research in this field are debated. miRNAs identified so far, whose expressions/activities are deregulated in NAFLD, and which contribute to the outcomes of this pathology are further reviewed. Finally, the potential therapeutic usages in a short to medium term of miRNA-based strategies in NAFLD, in particular to identify non-invasive biomarkers, or to design pharmacological analogues/inhibitors having a broad range of actions on hepatic metabolism, are highlighted.


Assuntos
MicroRNAs/fisiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/terapia , Humanos , Hepatopatia Gordurosa não Alcoólica/fisiopatologia
7.
Plant Physiol Biochem ; 142: 303-311, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31351321

RESUMO

microRNA393 (miR393) and its target module have been implicated as comprising a conserved mechanism to regulate developmental processes and plant growth in response to environmental signals through the auxin signaling pathway. Our previous work identified miR393 and its two targets in barley. In this study, we further investigated the expression pattern of miR393 and its biological functions in seedling growth and drought tolerance. We showed that the miR393 overexpressing line (OE) exhibited increased stomatal density with decreased guard cell length, while the miR393 knockdown line (MIM) displayed the opposite phenotype, which might be due to the effects of miR393 on AUXIN RESPONSE FACTOR5 (ARF5) and three stomatal development-related genes, such as EPIDERMAL PATTERNING FACTOR1 (EPF1), SPEECHLESS (SPCH), and MUTE. In addition, the MIM line conferred enhanced drought tolerance, with alleviated leaf chlorosis and lipid peroxidation after 22 days drought treatment. In contrast, the OE line was more sensitive to drought stress and accumulated more malondialdehyde and hydrogen peroxide than the wild type. Furthermore, polyethylene glycol (PEG) treatment-induced abscisic acid (ABA) accumulation in leaves was suppressed in the OE line, indicating that miR393 might regulate drought stress response and tolerance through its interaction with ABA biosynthesis. Overall, these data suggest that miR393 might be a potential target for manipulation of stomatal density and improvement of drought tolerance in barley.


Assuntos
Hordeum/fisiologia , MicroRNAs/fisiologia , Estômatos de Plantas/crescimento & desenvolvimento , RNA de Plantas/fisiologia , Plântula/crescimento & desenvolvimento , Ácido Abscísico/metabolismo , Desidratação , Regulação da Expressão Gênica de Plantas , Hordeum/crescimento & desenvolvimento , Hordeum/metabolismo , Reguladores de Crescimento de Planta/metabolismo , Folhas de Planta/crescimento & desenvolvimento
8.
Life Sci ; 232: 116648, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31301414

RESUMO

AIMS: Laminin γ2 (LAMC2) is over-expressed in ovarian cancer, and its high expression facilitates cell invasion. Nevertheless, the effects of LAMC2 on other ovarian cancer cell functions and its underlying mechanism remain largely unclear. Bioinformatics analysis shows that LAMC2 is a predicted target of miR-125a-5p and miR-193a-3p. Therefore, the present study aimed to investigate the effects of LAMC2 in ovarian cancer progression and determine whether LAMC2 expression is under the regulation of miR-125a-5p or miR-193a-3p in ovarian cancer. MATERIALS AND METHODS: Immunohistochemistry staining, western blot and qPCR were used to detect LAMC2 expression profiles. CCK-8, flow cytometry and tumour formation assays were used to assess cell proliferation, apoptosis and tumorigenesis. The interaction between miR-125a-5p/miR-193a-3p and LAMC2 were determined by the luciferase gene reporter assay. KEY FINDINGS: The results showed that LAMC2 was over-expressed in ovarian cancer tissues and cell lines. Over-expression of LAMC2 significantly promoted cell proliferation and repressed cell apoptosis, as well as increased the expression levels of p38, p-p38, c-myc and CREB, and translocated p38 protein to the nucleus. In addition, the promotion of cell proliferation and repression of cell apoptosis mediated by LAMC2 over-expression were all weakened when p38 was downregulated. Moreover, LAMC2 expression was negatively regulated by miR-125a-5p, which inhibited the nuclear accumulation of p38 protein. Upregulation of LAMC2 significantly abolished the effects of miR-125a-5p on cell proliferation inhibition and cell apoptosis promotion, as well as tumourigenesis repression. SIGNIFICANCE: The present study clarified that LAMC2 functioned as an oncogene in ovarian cancer through upregulating p38 under the regulation of miR-125a-5p.


Assuntos
Laminina/fisiologia , MicroRNAs/fisiologia , Neoplasias Ovarianas/patologia , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Progressão da Doença , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Ovarianas/enzimologia , Neoplasias Ovarianas/genética
9.
Life Sci ; 232: 116656, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31306658

RESUMO

AIMS: Tamoxifen-induced liver-specific Dicer1 deletion (iDicer1-/-) in mature mice may provide clues demonstrating the genuine effects of acute loss of Dicer1 and miRNAs in the liver regeneration process. MAIN METHODS: In this study, mice with tamoxifen-induced Dicer1 deletion through the Cre/LoxP system were constructed and then underwent classic 70% partial hepatectomy or CCl4-induced liver injury. To rescue the inhibitory effect of Dicer1 ablation on liver regeneration, miR-21 agomir was injected into the tail vein of iDicer1-/- mice. KEY FINDINGS: Unlike constitutive embryonic deletion of Dicer1, tamoxifen-induced Dicer1 deletion did not result in severe liver injury or lesions, providing an ideal model for investigating acute loss of Dicer1 and miRNAs in liver regeneration. Dicer1 deletion led to impaired liver regeneration through the inhibitory effect of miR-21 on PTEN and Rhob expression. SIGNIFICANCE: In our previous study, we found that embryonic loss of Dicer1 impairs hepatocyte survival and leads to chronic inflammation and progenitor cell activation, while the role of Dicer1 in liver regeneration remains largely unknown. We clearly identified the promotion effect of Dicer1 on liver regeneration by increasing miR-21 expression, which inhibits the expression of two negative cell proliferation regulators, Pten and Rhob.


Assuntos
RNA Helicases DEAD-box/fisiologia , Regeneração Hepática/fisiologia , MicroRNAs/fisiologia , PTEN Fosfo-Hidrolase/metabolismo , Ribonuclease III/fisiologia , Proteína rhoB de Ligação ao GTP/metabolismo , Animais , RNA Helicases DEAD-box/genética , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Camundongos , Camundongos Knockout , Ribonuclease III/genética , Tamoxifeno/administração & dosagem
10.
Life Sci ; 232: 116664, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31325426

RESUMO

AIMS: MicroRNAs have been demonstrated to be involved in the development of atherosclerosis. The present study aimed to evaluate the effect of miR-99a-5p and its target gene Homeobox A1 (HOXA1) in atherosclerosis. MAIN METHODS: The biological functions of miR-99a-5p on human aortic smooth muscle cells (ASMCs) were assessed by MTT, wound healing and transwell assays. The target genes of microRNAs were predicted by TargetScan and miRDB. The binding of miR-99a-5p and HOXA1 was confirmed by luciferase reporter assay. In the in vivo study, high-fat diet-induced atherosclerosis model was established in Apolipoprotein E knockout mice. Hematoxylin-eosin (H&E), oil Red O and Masson trichrome staining were performed for determination of atherosclerotic lesion. The levels of miR-99a-5p and HOXA1 mRNA were detected by real-time PCR. HOXA1 and migration-associated protein levels were detected by western blot or immunohistochemistry analysis. KEY FINDINGS: MiR-99a-5p inhibited HOXA1 expression by targeting 3'UTR of HOXA1 mRNA. Enforced HOXA1 significantly promoted the proliferation, migration, and invasion of ASMCs. Furthermore, miR-99a-5p overexpression inhibited the proliferation, migration, and invasion of ASMCs stimulated by HOXA1, whereas miR-99a-5p inhibition reversed the effects of HOXA1 knockdown on these behaviours of ASMCs. In vivo, the specific overexpression of miR-99a-5p significantly abated atherosclerotic lesions formatted, accompanied with a significant down-regulation of HOXA1 mRNA and protein expression levels. SIGNIFICANCE: We demonstrate for first time that miR-99a-5p may serve as a potential inhibitor of the atherosclerosis, and miR-99a-5p plays its role partially through targeting HOXA1.


Assuntos
Aterosclerose/prevenção & controle , Regulação da Expressão Gênica , Genes Homeobox , Proteínas de Homeodomínio/genética , MicroRNAs/fisiologia , Fatores de Transcrição/genética , Regiões 3' não Traduzidas , Animais , Aterosclerose/genética , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Proteínas de Homeodomínio/fisiologia , Humanos , Masculino , Camundongos , Camundongos Knockout , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Fatores de Transcrição/fisiologia
11.
Life Sci ; 232: 116676, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31340165

RESUMO

Bone is one of the most dynamic organs in the body that continuously undergoes remodeling through bone formation and resorption. A cascade of molecules and pathways results in the osteoblast differentiation that is attributed to osteogenesis, or bone formation. The process of osteogenesis is achieved through participation of the Wnt pathway, FGFs, BMPs/TGF-ß, and transcription factors such as Runx2 and Osx. The activity and function of the master transcription factor, Runx2, is of utmost significance as it can induce the function of osteoblast differentiation markers. A number of microRNAs [miRNAs] have been recently identified in the regulation of Runx2 expression/activity, thus affecting the process of osteogenesis. miRNAs that target Runx2 corepressors favor osteogenesis, while miRNAs that target Runx2 coactivators inhibit osteogenesis. In this review, we focus on the regulation of Runx2 by miRNAs in osteoblast differentiation and their potential for treating bone and bone-related diseases.


Assuntos
Diferenciação Celular/fisiologia , Subunidade alfa 1 de Fator de Ligação ao Core/fisiologia , MicroRNAs/fisiologia , Osteoblastos/citologia , Animais , Humanos
12.
Folia Histochem Cytobiol ; 57(2): 64-73, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31246264

RESUMO

INTRODUCTION: This study endeavors to analyze the effects of miR-1204 on the expression of DEK oncogene in non-small cell lung cancer (NSCLC) cell lines and to study the molecular mechanisms of these effects. MATERIAL AND METHODS: The miR-1204 mimics and inhibitors were transfected into the (A549 and SPC) NSCLC cells. Then the mRNA levels, cell viability, apoptosis rate, morphology and caspase activity were determined. The expression of apoptosis-related proteins Bcl-2 and Bax was also analyzed. RESULTS: In NSCLC cell lines (A549 and SPC), DEK mRNA levels were down-regulated in miR-1204 overex-pression group. In miR-1204 inhibition group, the expression of DEK mRNA showed an opposite trend. The overexpression of miR-1204 increases the apoptosis rate in NSCLC cells. The Bcl-2 levels in the miR-1204 over-expression group were decreased, while the Bax level was increased. In the miR-1204 inhibition group, expression of Bcl-2 and Bax showed opposite trends. Cell staining revealed cell's morphological changes; the apoptosis in the miR-1204 overexpression group revealed significant morphological features, such as brighter nuclei and nu-clear condensation. Results indicated a typical characteristic of apoptosis in the miR-1204 overexpression group. Caspase-9 and Caspase-3 were involved in the apoptosis pathway, which was mediated by miR-1204 and DEK. CONCLUSIONS: The miR-1204 induces apoptosis of NSCLC cells by inhibiting the expression of DEK. The mech-anism of apoptosis involves down-regulation of Bcl-2 and up-regulation of Bax expression. Moreover, the apoptosis was mediated by mitochondria-related caspase 9/3 pathway.


Assuntos
Apoptose/fisiologia , Carcinoma Pulmonar de Células não Pequenas/genética , Proteínas Cromossômicas não Histona/genética , Neoplasias Pulmonares/genética , MicroRNAs/fisiologia , Proteínas Oncogênicas/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , RNA Mensageiro/fisiologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Caspase 3/metabolismo , Caspase 8/metabolismo , Caspase 9/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Regulação para Cima , Proteína X Associada a bcl-2/metabolismo
13.
Artigo em Chinês | MEDLINE | ID: mdl-31177707

RESUMO

Objective: To investigate the regulatory effect of miR-29c on the trans-differentiation of pulmonary fibroblasts into myofibroblasts induced by silica dust. Methods: Fibroblasts obtained from SD rat lung tissue and pulmonary macrophages (NR8383) were co-cultured to establish the silicosis cell model in vitro. And real time-quantitative polymerase chain reaction (RT-qPCR) and Western Blot assays were performed to detect the altered expression level of miR-29c and α-smooth muscle actin (α-SMA) . After that, the in vitro cell model was transfected with corresponding viruses to establish miR-29c overexpression and inhibition cell models, and the mRNA and protein expression levels of α-SMA were detected simultaneously. Results: Compared with control group, the expression level of miR-29c in the silicosis cell model in vitro was down-regulated significantly after 12 or 18 h exposed to SiO(2), and both of the mRNA and protein expression levels of α-SMA were up-regulated instead (P<0.05) . When transfected with corresponding viruses, the mRNA and protein expression levels of α-SMA in the pulmonary fibroblasts were significantly up-regulated in miR-29c inhibition group and down-regulated in miR-29c overexpression group (P<0.05) . Conclusion: Based on the findings, it could be safely infered that the development of pulmonary fibrosis could be impeded by inhibiting transdifferentiation process of pulmonary fibroblasts into myofibroblasts regulated by miR-29c, miR-29c could be an potential therapeutic target to lung fibrosis induced by silica.


Assuntos
Transdiferenciação Celular , MicroRNAs , Animais , Fibroblastos , MicroRNAs/fisiologia , Ratos , Ratos Sprague-Dawley , Dióxido de Silício/toxicidade
14.
Plant Sci ; 285: 68-78, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31203895

RESUMO

The miR169 family, a large-scale microRNA gene family conserved in plants, is involved in stress responses, although how soybean miR169 functions in response to drought stress remains unclear. We show that gma-miR169c exerts a negative regulatory role in the response to drought stress by inhibiting the expression of its target gene, nuclear factor Y-A (NF-YA). A real-time RT-PCR analysis indicated that gma-miR169c is widely expressed in soybean tissues and induced by polyethylene glycol (PEG), high salt, cold stress and abscisic acid (ABA). Histochemical ß-glucuronidase (GUS) staining showed that the gma-miR169c promoter drives GUS reporter gene expression in various transgenic Arabidopsis tissues, and the stress-induced pattern was confirmed in transgenic Arabidopsis and transgenic soybean hairy roots. Arabidopsis overexpressing gma-miR169c is more sensitive to drought stress, with reduced survival, accelerated leaf water loss, and shorter root length than wild-type plants. We identified a precise cleavage site for 10 gma-miR169c targets and found reduced transcript levels of the AtNFYA1 and AtNFYA5 transcription factors in gma-miR169c-overexpressing Arabidopsis and reduced expression of the stress response genes AtRD29A, AtRD22, AtGSTU25 and AtCOR15A. These results indicate that gma-miR169c plays a negative regulatory role in drought stress and is a candidate miRNA for improving plant drought adaptation.


Assuntos
MicroRNAs/genética , Soja/genética , Arabidopsis/genética , Desidratação , MicroRNAs/fisiologia , Folhas de Planta/fisiologia , Raízes de Plantas/fisiologia , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase em Tempo Real , Soja/fisiologia
15.
Infect Immun ; 87(8)2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31182615

RESUMO

CD4+ T helper 1 (Th1) cells producing interferon gamma (IFN-γ) are critical for the resolution of visceral leishmaniasis (VL). MicroRNA 155 (miR155) promotes CD4+ Th1 responses and IFN-γ production by targeting suppressor of cytokine signaling-1 (SOCS1) and Src homology-2 domain-containing inositol 5-phosphatase 1 (SHIP-1) and therefore could play a role in the resolution of VL. To determine the role of miR155 in VL, we monitored the course of Leishmania donovani infection in miR155 knockout (miR155KO) and wild-type (WT) C57BL/6 mice. miR155KO mice displayed significantly higher liver and spleen parasite loads than WT controls and showed impaired hepatic granuloma formation. However, parasite growth eventually declined in miR155KO mice, suggesting the induction of a compensatory miR155-independent antileishmanial pathway. Leishmania antigen-stimulated splenocytes from miR155KO mice produced significantly lower levels of Th1-associated IFN-γ than controls. Interestingly, at later time points, levels of Th2-associated interleukin-4 (IL-4) and IL-10 were also lower in miR155KO splenocyte supernatants than in WT mice. On the other hand, miR155KO mice displayed significantly higher levels of IFN-γ, iNOS, and TNF-α gene transcripts in their livers than WT mice, indicating that distinct organ-specific antiparasitic mechanisms were involved in control of L. donovani infection in miR155KO mice. Throughout the course of infection, organs of miR155KO mice showed significantly more PDL1-expressing Ly6Chi inflammatory monocytes than WT mice. Conversely, blockade of Ly6Chi inflammatory monocyte recruitment in miR155KO mice significantly reduced parasitic loads, indicating that these cells contributed to disease susceptibility. In conclusion, we found that miR155 contributes to the control of L. donovani but is not essential for infection resolution.


Assuntos
Leishmania donovani , Leishmaniose Visceral/imunologia , MicroRNAs/fisiologia , Animais , Granuloma/etiologia , Interferon gama/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Monócitos/fisiologia , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/fisiologia
16.
Plant Sci ; 284: 73-81, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31084881

RESUMO

Storage tuber and root crops make up a significant portion of the world's subsistence food supply. Because of their importance in food security, yield enhancement has become a priority. A major focus has been to understand the biology of belowground storage organ development. Considerable insights have been gained studying tuber development in potato. We now know that two mobile signals, a full-length mRNA, StBEL5, and a protein, StSP6A, play pivotal roles in regulating tuber development. Under favorable conditions, these signals move from leaves to a belowground modified stem (stolon) and regulate genes that activate tuberization. Overexpression of StBEL5 or StSP6A increases tuber yield even under non-inductive conditions. The mRNAs of two close homologs of StBEL5, StBEL11 and StBEL29, are also known to be mobile but act as repressors of tuberization. Polypyrimidine tract-binding proteins (PTBs) are RNA-binding proteins that facilitate the movement of these mRNAs. Considering their role in tuberization, it is possible that these mobile signals play a major role in storage root development as well. In this review, we explore the presence of these signals and their relevance in the development and yield potential of several important storage root crops.


Assuntos
Raízes de Plantas/crescimento & desenvolvimento , Tubérculos/crescimento & desenvolvimento , MicroRNAs/metabolismo , MicroRNAs/fisiologia , Floema/metabolismo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/fisiologia , Transdução de Sinais/fisiologia
17.
Plant Sci ; 284: 99-107, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31084885

RESUMO

Phloem-mobile mRNAs are assumed to contain sequence elements directing RNA to the phloem translocation pathway. One of such elements is represented by tRNA sequences embedded in untranslated regions of many mRNAs, including those proved to be mobile. Genomic RNAs of a number of plant viruses possess a 3'-terminal tRNA-like structures (TLSs) only distantly related to genuine tRNAs, but nevertheless aminoacylated and capable of interaction with some tRNA-binding proteins. Here, we elaborated an experimental system for analysis of RNA phloem transport based on an engineered RNA of Potato virus X capable of replication, but not encapsidation and movement in plants. The TLSs of Brome mosaic virus, Tobacco mosaic virus and Turnip yellow mosaic virus were demonstrated to enable the phloem transport of foreign RNA. A miRNA precursor, pre-miR390b, was also found to render RNA competent for the phloem transport. In line with this, sequences of miRNA precursors were identified in a Cucurbita maxima phloem transcriptome, supporting the hypothesis that, at least in some cases, miRNA phloem signaling can involve miRNA precursors. Collectively, the data presented here suggest that RNA molecules can be directed into the phloem translocation pathway by structured RNA elements such as those of viral TLSs and miRNA precursors.


Assuntos
MicroRNAs/metabolismo , Floema/metabolismo , RNA de Plantas/metabolismo , RNA de Transferência/metabolismo , Bromovirus/metabolismo , Cucurbita/metabolismo , Cucurbita/virologia , MicroRNAs/fisiologia , Floema/fisiologia , Potexvirus/metabolismo , RNA de Transferência/fisiologia , Vírus do Mosaico do Tabaco/metabolismo , Tymovirus/metabolismo
18.
Plant Sci ; 283: 60-69, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31128716

RESUMO

The miR156/miR529-SPL module acts a vital role in regulating plant growth and development. Though miR535 shows very high sequence identity to miR156 and miR529, it is still unknown whether miR535 could control plant growth and development. In this study, we performed the evolutionary analyses of miR535s in land plants and found that miR535s were less conserved than miR156s during evolution. In rice, miR535 expressed at a very low level during the vegetative growth but highly accumulated in young panicles, which is similar with OsmiR529, but opposite to OsmiR156. Expectedly, OsmiR535 overexpression in rice reduced plant height by decreasing the 1st and 2nd internode length. Furthermore, OsmiR535 overexpression imposed great influence in panicle architecture, such as more but shorter panicles, and fewer primary/secondary panicle branches. Moreover, OsmiR535 overexpression increased the grain length, but did not affect grain width. Through quantitative real-time PCR analyses, we further revealed that OsmiR535 overexpression repressed the expression of OsSPL7/12/16, as well as the OsSPLs downstream panicle related genes, including OsPIN1B, OsDEP1, OsLOG and OsSLR1. Taken together, our findings suggest that OsmiR535 multiply modulates plant height, panicle architecture and grain shape possibly by regulating OsSPLs genes in rice.


Assuntos
Grão Comestível/crescimento & desenvolvimento , MicroRNAs/fisiologia , Oryza/crescimento & desenvolvimento , Grão Comestível/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Oryza/anatomia & histologia , Oryza/genética , Oryza/metabolismo , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase em Tempo Real , Alinhamento de Sequência , Análise de Sequência de RNA
19.
Gene ; 706: 91-96, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31054362

RESUMO

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in reproductive-aged women. Clinical manifestations include hyperandrogenism, chronic anovulation, polycystic ovaries and being frequently accompanied by insulin resistance (IR) and obesity. MicroRNAs (miRNAs) are short non-coding RNAs which are involved in the regulation of gene expression at the post-transcriptional level. Altered miRNAs levels have been showed to be associated with a variety of diseases including diabetes, endometriosis and cancer. In recent years, more and more evidence suggests abnormal expression of miRNAs are detected in granulosa cells, theca cells, adipose tissue, follicular fluid, serum and peripheral blood leukocytes of women with PCOS and display vital role in the occurrence and development of PCOS. This will shed light on new strategies for the diagnosis and treatment of this syndrome. In this paper, we will review the recent research on miRNAs with respect to PCOS.


Assuntos
MicroRNAs/genética , MicroRNAs/fisiologia , Síndrome do Ovário Policístico/genética , Adulto , Feminino , Regulação da Expressão Gênica , Humanos , Resistência à Insulina , Pessoa de Meia-Idade , Obesidade , Síndrome do Ovário Policístico/fisiopatologia
20.
Gene ; 706: 124-130, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31077735

RESUMO

In this study, we constructed a tumor necrosis factor α (TNF-α)-induced synovial cell inflammatory model using human synoviocytes (HS) cell line to explore the function of miR-98 in rheumatoid arthritis (RA). miR-98 mimics or miR-98 inhibitor were transfected into HS cells to up-regulate or down-regulate the expression of miR-98. The proliferation and apoptosis of HS cells were determined using CCK8 assay and flow cytometry, respectively. TargetScan website was utilized to predict the targets of miR-98. Luciferase assay was carried out to verify that IL-10 is a target of miR-98. Western blot was performed to analyze the expression of IL-10, apoptosis-related and NF-κB signaling pathway-related proteins. Our results demonstrated that the expression of miR-98 was up-regulated in HS cells stimulated by TNF-α. Down-regulation of miR-98 by inhibitor in TNF-α-stimulated HS cells dramatically inhibited cell proliferation and promoted cell apoptosis compared with the miR-98 inhibitor NC group. The protein expression of Bcl-2 was declined while the levels of Bax and Bim were increased by miR-98 inhibitor in TNF-α-stimulated HS cells. IL-10 was predicted and verified as a target of miR-98. qRT-PCR and western blot results revealed that the level of IL-10 was negatively regulated by miR-98. Finally, we identified that down-regulation of miR-98 reduced the expression level of p-p65 and p-IκBα in TNF-α-stimulated HS cells. In summary, our present study demonstrated that down-regulation of miR-98 inhibited the proliferation and promoted the apoptosis of TNF-α-stimulated HS partly by targeting IL-10 and regulating NF-κB signaling pathway, insinuating miR-98 as a candidate biomarker in RA.


Assuntos
Apoptose/genética , MicroRNAs/genética , MicroRNAs/fisiologia , Artrite Reumatoide/genética , Linhagem Celular , Proliferação de Células/fisiologia , Fibroblastos/metabolismo , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , MicroRNAs/metabolismo , Modelos Biológicos , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/fisiologia , Membrana Sinovial/metabolismo , Sinoviócitos/metabolismo , Sinoviócitos/fisiologia , Fator de Transcrição RelA/metabolismo , Ativação Transcricional , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/fisiologia , Regulação para Cima
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