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1.
Shanghai Kou Qiang Yi Xue ; 29(3): 267-274, 2020 Jun.
Artículo en Chino | MEDLINE | ID: mdl-33043343

RESUMEN

PURPOSE: To investigate the molecular mechanism of LncRNA NEAT1 regulating proliferation, migration and invasion of tongue squamous cell carcinoma cells by regulating miR-339-5p/ITGA3 axis. METHODS: qRT-PCR and Western blot were used to detect the expression of NEAT1, miR-339-5p, ITGA3 mRNA and ITGA3 protein in 25 cases of human tongue squamous cell carcinoma, its corresponding adjacent tissues, human normal oral mucosal cell line HOK and human tongue squamous cell carcinoma cell lines TSCCA, CAL27, SCC15 and HN13. CAL27 cell lines that inhibited NEAT1 and overexpressed miR-339-5p were constructed, respectively. Cell viability was detected by MTT assay, cell numbers of migration and invasion were detected by Transwell assay, and the expression of Cyclin D1 and MMP-9 proteins were detected by Western blotting. The dual luciferase reporter gene was used to verify the targeting relationship of NEAT1, miR-339-5p and ITGA3, and the regulatory relationship was detected by Western blotting and qRT-PCR. SPSS 17.0 software package was used for statistical analysis of the data. RESULTS: Compared with normal human oral mucosal cell line HOK, the expression of NEAT1 and ITGA3 was up-regulated, while the expression of miR-339-5p was down-regulated in human tongue squamous cell carcinoma cell lines. Inhibition of NEAT1 or over-expression of miR-339-5p significantly inhibited proliferation, migration and invasion of CAL27 cells, and significantly inhibited expression of Cyclin D1 and MMP-9 proteins. Dual luciferase reporter gene assay confirmed that NEAT1 directly interacted with miR-339-5p and suppressed its expression. miR-339-5p negatively regulated ITGA3 expression. Inhibition of NEAT1 reversed the inhibitory effect of the inhibition of miR-339-5p on proliferation, migration and invasion of CAL27 cells. CONCLUSIONS: LncRNA NEAT1 promotes proliferation, migration and invasion of tongue squamous cell carcinoma cells by down-regulating miR-339-5p/ITGA3 axis.


Asunto(s)
Carcinoma de Células Escamosas , MicroARNs , ARN Largo no Codificante/fisiología , Carcinoma de Células Escamosas/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Integrina alfa3 , MicroARNs/genética , ARN Largo no Codificante/genética
2.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(9): 1136-1141, 2020.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-33051430

RESUMEN

Preeclampsia is a multisystem disorder clinical syndrome, coexisting hypertension and proteinuria. It is a result of the shallow remodeling of the spiral arteries after 20 weeks of gestation, which changes the placental microenvironment and releases a series of maternal circulation factors. Currently, there are no effective tools for the treatment of preeclampsia unless terminating pregnancy. The unclear pathogenesis, the high rate of fetal growth restriction, fetal disability and maternal mortality make it important for researchers to explore the pathogenesis of preeclampsia. MicroRNAs (miRNAs) play an important role in regulating the expression of almost 30% of all genes by binding to the 3' untranslated region of a target mRNA, which affects various cell processes, including differentiation, proliferation, apoptosis, and development. A large number of miRNAs can be expressed in human placental tissues, while some are only specifically expressed and can also be released into the maternal blood in the form of exosome during pregnancy. Thus, it makes miRNA hopefully as a novel molecular marker for monitoring pregnancy, prediction and diagnosis of gestational diseases.


Asunto(s)
MicroARNs , Preeclampsia , Femenino , Retardo del Crecimiento Fetal , Humanos , MicroARNs/genética , Placenta , Preeclampsia/genética , Embarazo , ARN Mensajero
3.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5312-5315, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-33019183

RESUMEN

With cancer being one of the main remaining challenges of modern medicine, a lot of effort is put towards oncology research. Since early diagnosis is a highly important factor for the treatment of many types of cancer, screening tests have become a popular research subject. Technical and technological advances have brought down the price of genome sequencing and have led to an increase in understanding the relationship between DNA, RNA and tumor sites. These advances have sparked an interest in personalized and precision medicine research. In this work, we propose a deep neural network classifier to identify the anatomical site of a tumor. Using 27 TCGA miRNA stem-loops cohorts, we classify tumors in 20 anatomical sites with a 96.9% accuracy. Our results demonstrate the possibility of using stem-loop expression data for accurate cancer localization.


Asunto(s)
MicroARNs , Neoplasias , Aprendizaje Profundo , Humanos , MicroARNs/genética , Neoplasias/diagnóstico , Redes Neurales de la Computación , Medicina de Precisión
4.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5320-5325, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-33019185

RESUMEN

In addition to socioeconomic influences, biological factors are believed to play a role in health disparities. In this paper, we investigate miRNA, mRNA, and DNA methylation patterns that contribute to disparities in hepatocellular carcinoma (HCC). This is accomplished by integration of mRNA-Seq, miRNA-Seq, and DNA methylation data we acquired by analysis of liver tissues from 30 HCC patients consisting of European Americans (EAs), African Americans (AAs), and Asian Americans (Asians). Mixed-ANOVA models are applied to identify miRNAs, mRNAs, and DNA methylation sites that are significantly altered in tumor vs. adjacent normal tissues in a race-specific manner. Through integrated analysis, a refined list of differentially expressed mRNAs is obtained by selecting those that are targets of differentially expressed miRNAs and consist of promoter regions that are differentially methylated.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroARNs , Carcinoma Hepatocelular/genética , Epigénesis Genética , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/genética , MicroARNs/genética
5.
Epidemiol Mikrobiol Imunol ; 69(3): 116-120, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33086852

RESUMEN

BACKGROUND: RNase L is known as a terminal component of antiviral and Interferon (IFN) pathways in mammalian cells. On the other hand, the human miR-29 family of microRNAs (miRs) has three mature members, miR-29a, miR-29b, and miR-29c. miR-29 is encoded by two gene clusters and the family members have multifunctional roles in various biological processes. OBJECTIVES: To determine the potential role of miR-29 in the regulation of RNASEL gene expression by designing inhibitors against its targeting miRNA, miR-29a-3p and evaluate the RNase L expression. MATERIAL AND METHODS: After selecting miR-29a-3p as a main regulating miRNA for RNASEL in silico, two inhibitors were designed against it and synthesized. Synthesized strands were made double-stranded DNA oligos, treated with T4 polynucleotide kinase (PNK), cloned into the pCDH-CMV-MCS-EF1-cGFP-T2A-Puro vector and transformed into DH5α. Colony PCR and sequencing was done for affirmation. Then the miR-29a-3p inhibitors were transfected into HEK-293T cell line and RNASEL gene expression was analyzed. RESULTS: The miR-29a-3p inhibitors decreased miR-29a-3p expression in vitro. In addition, miR-29a-3p expression reduction resulted in an increase of RNASEL gene expression. CONCLUSIONS: miR-29a-3p inhibitors could increase in RNASEL gene expression which potentially affects the antiviral/IFN pathway. The inhibitors could be considered as drug candidates in different diseases especially viral infections.


Asunto(s)
Endorribonucleasas/genética , MicroARNs/genética , Expresión Génica , Células HEK293 , Humanos
6.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 2346-2352, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-33018478

RESUMEN

Lung cancer is a major public health burden and among the highest incidence and mortality rates of the cancers. MicroRNAs (miRNAs) play an important role in the development of lung cancer. The aim of this study was to investigate whether there was a potential causal relation between miRNAs and non-small-cell lung cancer (NSCLC). 1,026 patients with NSCLC from The Cancer Genome Atlas (TCGA) were analyzed. NSCLC associated SNPs' allele scores were established, and candidate miRNAs were filtered from differential expression analysis. Mendelian randomization (MR) analysis was conducted for 5 candidate miRNA (hsa-miR-135b, hsa-miR-142, hsa-miR-182, hsa-miR-183 and hsa-miR-3607) and 76 candidate SNPs in lung adenocarcinoma (LUAD) group. According to the core assumptions of MR, there was no clear evidence of a causal relation between the 5 candidate miRNAs and LUAD. The reads per million miRNAs mapped (RPM) level of candidate miRNAs changed less than 3% per allele score. To our knowledge, this is the first study using the TCGA data set to investigate the causal relation between miRNAs and lung cancer using the MR approach, and also one of the first MR studies to use miRNA expression as an exposure factor, with the SNPs as instrumental variables.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , Biomarcadores de Tumor , Carcinoma de Pulmón de Células no Pequeñas/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Análisis de la Aleatorización Mendeliana , MicroARNs/genética , Nucleótidos , Polimorfismo de Nucleótido Simple
7.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(10): 1332-1340, 2020 Oct 15.
Artículo en Chino | MEDLINE | ID: mdl-33063501

RESUMEN

Objective: To summarize the research progress of the regulatory role of microRNA (miRNA) in osteogenic differentiation of mesenchymal stem cells (MSCs) and its application as a therapeutic target and diagnostic tool in orthopedic diseases. Methods: The recent literature on the regulation of MSCs osteogenic differentiation by miRNAs was extensively reviewed, and its regulatory mechanism and its application as a therapeutic target and diagnostic tool in orthopedic diseases were reviewed. Results: miRNAs are small endogenous non-coding RNAs with a length of 20-22 nucleotides, which play an important role in the osteogenic differentiation of MSCs. Osteogenesis begins with the differentiation of MSCs into mature osteoblasts, and each stage of dynamic homeostasis of bone metabolism is associated with the regulation of different miRNAs. miRNAs are regulated from the post-transcriptional level by mRNAs cleavage, degradation, translational repression, or methylation. In addition, current studies suggest that miRNAs can be used as a new diagnostic tool and therapeutic target for orthopedic diseases. Conclusion: Further study on the regulation mechanism of miRNAs will provide more ideas for finding new therapeutic targets and diagnostic tools for orthopedic disease.


Asunto(s)
Células Madre Mesenquimatosas , MicroARNs , Diferenciación Celular , MicroARNs/genética , Osteoblastos , Osteogénesis
8.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1523-1527, 2020 Oct.
Artículo en Chino | MEDLINE | ID: mdl-33067948

RESUMEN

OBJECTIVE: To investigate the expression of Hsa-miR-9 in children with acute lymphoblastic leukemia (ALL) and its relationship with CDX2 gene. METHODS: The clinical data of 130 patients with ALL were collected from nearly five years in our hospital, and in the same period 60 healthy children in the same age were selected as control group. Real-time fluorescent quantitative PCR (qRT-PCR) was applied to examine the expression of Hsa-miR-9 and CDX2 gene of the two groups, the relationship between Hsa-miR-9 expression and ALL patients' clinical characteristics, survival time, CDX2 expression were analyzed. RESULTS: The expression level of Hsa-miR-9 in ALL children was significantly lower than that in the healthy control group (P<0.001). The expression of Hsa-miR-9 in ALL children related with serum WBC, infiltrating lymph nodes, splenomegaly, and risk grade (P<0.05). The median survival time of ALL children with high expression of Hsa-miR-9 was significantly longer than that of the ALL children with low expression (P<0.001). Hsa-miR-9 expression significantly correlated with CDX2 gene expression in ALL children at different treatment stages (P<0.05). CONCLUSION: The expression of Hsa-miR-9 decreases in children with ALL, and ALL children with high expression of Hsa-miR-9 have a longer overall survival time. The expression of hsa-miR-9 in ALL children closely related with CDX2 gene.


Asunto(s)
MicroARNs , Leucemia-Linfoma Linfoblástico de Células Precursoras , Factor de Transcripción CDX2/genética , Niño , Humanos , MicroARNs/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Reacción en Cadena en Tiempo Real de la Polimerasa
9.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1578-1584, 2020 Oct.
Artículo en Chino | MEDLINE | ID: mdl-33067957

RESUMEN

OBJECTIVE: To investigate the potential mechanisms of miR-224 affecting the proliferation and invasion of diffuse large B-cell lymphoma (DLBCL) cells. METHODS: The blood samples of 76 DLBCL patients(DLBCL group) diagnosed at the First Affiliated Hospital of Kunming Medical University from June 2011 to December 2017, and 41 healthy persons of physical examination (normal control group) as well as human lymphatic endothelial cells (HELC) and DLBCL cell lines HBL1, OCI-LY10, OCI-LY8, OCI-LY19 were collected. The expression of miR-224 and PIK3CD mRNA was measured by RT-qPCR. The proliferation of HBL1 cells was detected by CCK-8 method and colony formation test. The invasion ability of HBL1 cells was detected by Transwell test. Dual-luciferase reporter gene assay was used to verify the relationship between miR-224 and PIK3CD. The expression of PIK3CD protein was measured by Western blot. RESULTS: The expression of miR-224 in blood of DLBCL patients was very significantly lower than that in normal control group (P<0.01). The overexpression of miR-224 significantly decreased proliferation and invasion of HBL1 cells (all P<0.01). PIK3CD was a target gene of miR-224. Knockdown of PIK3CD significantly suppressed the proliferation and invasion of HBL1 cells (all P<0.01). CONCLUSION: MiR-224 plays a key role in the progression of DLBCL, and the proliferation and invasion of HBL1 cells can be suppressed by targeted inhibition of PIK3CD.


Asunto(s)
Linfoma de Células B Grandes Difuso , MicroARNs , Línea Celular Tumoral , Proliferación Celular , Fosfatidilinositol 3-Quinasa Clase I/genética , Células Endoteliales , Humanos , Linfoma de Células B Grandes Difuso/genética , MicroARNs/genética
10.
Nat Commun ; 11(1): 4964, 2020 10 02.
Artículo en Inglés | MEDLINE | ID: mdl-33009394

RESUMEN

Thrombosis leads to platelet activation and subsequent degradation; therefore, replenishment of platelets from hematopoietic stem/progenitor cells (HSPCs) is needed to maintain the physiological level of circulating platelets. Platelet-derived microparticles (PMPs) are protein- and RNA-containing vesicles released from activated platelets. We hypothesized that factors carried by PMPs might influence the production of platelets from HSPCs, in a positive feedback fashion. Here we show that, during mouse acute liver injury, the density of megakaryocyte in the bone marrow increases following an increase in circulating PMPs, but without thrombopoietin (TPO) upregulation. In vitro, PMPs are internalized by HSPCs and drive them toward a megakaryocytic fate. Mechanistically, miR-1915-3p, a miRNA highly enriched in PMPs, is transported to target cells and suppresses the expression levels of Rho GTPase family member B, thereby inducing megakaryopoiesis. In addition, direct injection of PMPs into irradiated mice increases the number of megakaryocytes and platelets without affecting TPO levels. In conclusion, our data reveal that PMPs have a role in promoting megakaryocytic differentiation and platelet production.


Asunto(s)
Plaquetas/metabolismo , Diferenciación Celular , Micropartículas Derivadas de Células/metabolismo , Megacariocitos/citología , MicroARNs/metabolismo , Animales , Secuencia de Bases , Línea Celular , Endocitosis , Perfilación de la Expresión Génica , Humanos , Hígado/lesiones , Hígado/patología , Masculino , Megacariocitos/metabolismo , Ratones Endogámicos C57BL , Ratones Transgénicos , MicroARNs/genética , Poliploidía , Proteína de Unión al GTP rhoB/metabolismo
11.
Mol Genet Genomics ; 295(6): 1547-1558, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32915308

RESUMEN

MicroRNAs (miRNAs) are key in the post-transcriptional regulation of gene expression and thus characterization of miRNAs and investigation of the relative abundance and specificity of tissue expression are essential for understanding gene expression in the golden snub-nosed monkey (GSM, Rhinopithecus roxellanae). Here, we report the first dataset of GSM miRNAs where we identified 460 miRNAs in seven tissues, with 246 conserved known mature miRNAs and 214 novel mature miRNAs. We determined miRNA abundance and expression in the seven tissues using a Tissue Specificity Index score and found that most novel GSM miRNAs showed a highly tissue-specific expression pattern. In particular, 67 novel miRNAs and the miR-34 family were expressed in abundance only in the lung. Five known miRNAs were highly abundant in digestive organs such as the pancreas and liver, and four novel miRNAs were highly expressed in the heart and muscle. Annotation of target genes of GSM miRNAs indicated that target genes were enriched in many important pathways, such as the HIF-1 signaling pathway and xenobiotic biodegradation-related pathways. Collectively, these results emphasize that miRNAs play important roles in GSM diet and high-elevation adaptation regulation. In summary, this study provides essential information on GSM miRNAs and will benefit further investigations of the function and mechanism of miRNAs in controlling gene expression in the GSM.


Asunto(s)
Adaptación Fisiológica , Colobinae/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , MicroARNs/genética , Animales , Masculino , Especificidad de Órganos
12.
BMC Bioinformatics ; 21(1): 396, 2020 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-32894041

RESUMEN

BACKGROUND: MicroRNAs are a class of important small noncoding RNAs, which have been reported to be involved in the processes of tumorigenesis and development by targeting a few genes. Existing studies show that the imbalance between cell proliferation and apoptosis is closely related to the initiation and development of cancers. However, the impact of miRNAs on this imbalance has not been studied systematically. RESULTS: In this study, we first construct a cell fate miRNA-gene regulatory network. Then, we propose a systematical method for calculating the global impact of miRNAs on cell fate genes based on the shortest path. Results on breast cancer and liver cancer datasets show that most of the cell fate genes are perturbed by the differentially expressed miRNAs. Most of the top-identified miRNAs are verified in the Human MicroRNA Disease Database (HMDD) and are related to breast and liver cancers. Function analysis shows that the top 20 miRNAs regulate multiple cell fate related function modules and interact tightly based on their functional similarity. Furthermore, more than half of them can promote sensitivity or induce resistance to some anti-cancer drugs. Besides, survival analysis demonstrates that the top-ranked miRNAs are significantly related to the overall survival time in the breast and liver cancers group. CONCLUSION: In sum, this study can help to systematically study the important role of miRNAs on proliferation and apoptosis and thereby uncover the key miRNAs during the process of tumorigenesis. Furthermore, the results of this study will contribute to the development of clinical therapy based miRNAs for cancers.


Asunto(s)
Apoptosis/genética , Proliferación Celular/genética , MicroARNs/metabolismo , Biomarcadores/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Bases de Datos Genéticas , Femenino , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , MicroARNs/genética , ARN Mensajero/metabolismo , Análisis de Supervivencia
13.
Pestic Biochem Physiol ; 170: 104700, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32980067

RESUMEN

Argonautes (Ago) are important core proteins in RNA interference (RNAi) pathways of eukaryotic cells. Generally, it is thought that Ago1, Ago2 and Ago3 are involved in the miRNA (microRNA), siRNA (small interfering RNA) and piRNA (Piwi-interacting RNA)-mediated RNAi pathways, respectively. As a main component of the RNA-induced silencing complex (RISC), Ago2 plays an indispensable role in using siRNA to recognize and cut target messenger RNAs resulting in suppression of transcript levels, but the contributions of Ago1 and Ago3 to the siRNA-mediated RNAi pathway remain to be explored in many insect species. In this study, we investigated the contributions of four Ago genes (named LmAgo1, LmAgo2a and LmAgo2b and LmAgo3) to RNAi efficiency in Locusta migratoria by using both in vivo and in vitro experiments. Our results showed that suppression of each of the Ago genes significantly impaired RNAi efficiency when targeting Lmß-tubulin transcripts, resulting in recovery of 48, 43.3, 61.4 or 26% of Lmß-tubulin transcripts following RNAi-mediated suppression of LmAgo1, LmAgo2a, LmAgo2b, and LmAgo3, respectively. Furthermore, overexpression of LmAgo1, LmAgo2a, LmAgo2b, or LmAgo3 in a PAc5.1-V5/HisB vector and co-transfection with psicheck2 fluorescence vector in S2 cells reduced luciferase fluorescence by 38.3, 58.9, 53.3 or 55.6%, respectively. Taken together, our results showed that LmAgo1, LmAgo2a, LmAgo2b, and LmAgo3 each make significant contributions to RNAi efficiency in L. migratoria and suggest that the involvement of all four enzymes could be one of the major factors supporting robust RNAi responses observed in this species.


Asunto(s)
Locusta migratoria/genética , MicroARNs/genética , Animales , Proteínas Argonauta/genética , Interferencia de ARN , ARN Bicatenario/genética , ARN Interferente Pequeño/genética
14.
Int J Mol Sci ; 21(17)2020 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-32872332

RESUMEN

Acute Respiratory Distress Syndrome (ARDS) causes up to 40% mortality in humans and is difficult to treat. ARDS is also one of the major triggers of mortality associated with coronavirus-induced disease (COVID-19). We used a mouse model of ARDS induced by Staphylococcal enterotoxin B (SEB), which triggers 100% mortality, to investigate the mechanisms through which Δ9-tetrahydrocannabinol (THC) attenuates ARDS. SEB was used to trigger ARDS in C3H mice. These mice were treated with THC and analyzed for survival, ARDS, cytokine storm, and metabolome. Additionally, cells isolated from the lungs were used to perform single-cell RNA sequencing and transcriptome analysis. A database analysis of human COVID-19 patients was also performed to compare the signaling pathways with SEB-mediated ARDS. The treatment of SEB-mediated ARDS mice with THC led to a 100% survival, decreased lung inflammation, and the suppression of cytokine storm. This was associated with immune cell apoptosis involving the mitochondrial pathway, as suggested by single-cell RNA sequencing. A transcriptomic analysis of immune cells from the lungs revealed an increase in mitochondrial respiratory chain enzymes following THC treatment. In addition, metabolomic analysis revealed elevated serum concentrations of amino acids, lysine, n-acetyl methionine, carnitine, and propionyl L-carnitine in THC-treated mice. THC caused the downregulation of miR-185, which correlated with an increase in the pro-apoptotic gene targets. Interestingly, the gene expression datasets from the bronchoalveolar lavage fluid (BALF) of human COVID-19 patients showed some similarities between cytokine and apoptotic genes with SEB-induced ARDS. Collectively, this study suggests that the activation of cannabinoid receptors may serve as a therapeutic modality to treat ARDS associated with COVID-19.


Asunto(s)
Apoptosis/efectos de los fármacos , Betacoronavirus/fisiología , Agonistas de Receptores de Cannabinoides/uso terapéutico , Infecciones por Coronavirus/tratamiento farmacológico , Citocinas/inmunología , Dronabinol/uso terapéutico , Neumonía Viral/tratamiento farmacológico , Síndrome de Dificultad Respiratoria del Adulto/tratamiento farmacológico , Anciano , Animales , Líquido del Lavado Bronquioalveolar/inmunología , Infecciones por Coronavirus/mortalidad , Infecciones por Coronavirus/virología , Enterotoxinas/efectos adversos , Femenino , Humanos , Pulmón/inmunología , Pulmón/virología , Masculino , Ratones , Ratones Endogámicos C3H , MicroARNs/genética , Persona de Mediana Edad , Pandemias , Neumonía/tratamiento farmacológico , Neumonía/virología , Neumonía Viral/mortalidad , Neumonía Viral/virología , Síndrome de Dificultad Respiratoria del Adulto/mortalidad , Síndrome de Dificultad Respiratoria del Adulto/virología , Transducción de Señal/efectos de los fármacos
15.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(4): 499-505, 2020 Apr 30.
Artículo en Chino | MEDLINE | ID: mdl-32895132

RESUMEN

OBJECTIVE: To explore the effects of olmesartan on age-associated migration and invasion capacities and microRNA (miRAN) axis in human aortic vascular smooth muscle cells (HA-VSMCs). METHODS: Cultured HA-VSMCs were divided into control group, bleomycin-mediated senescence (BLM) group and bleomycin + olmesartan treatment group. Wound-healing assay and Boyden chambers invasion assay were used to assess the changes in migration and invasion of the cells, gelatin zymography was used to analyze matrix metalloproteinase-2 (MMP-2) activation in the cells. The differentially expressed miRNAs were identified by miRNA microarray assay and validated by quantitative real-time PCR. MiR-3133 inhibitor was used to examine the effects of molecular manipulation of olmesartan on age-associated migration and invasion and MMP-2 activation in the cells. RESULTS: Compared with those of the control group, the percentage of the repopulated cells and the number of cells crossing the basement membrane increased significantly in BLM group [(78.43±12.76)% vs (42.47±7.22)%, P < 0.05; 33.33±5.51 vs 13.00±4.36, P < 0.05]. A significant increase of MMP-2 activation was found in BLM group as compared with the control group (1.66 ± 0.27 vs 0.87 ± 0.13, P < 0.05). Olmesartan significantly inhibited BLM-induced enhancement of cell migration and invasion and MMP-2 secretion in the cells. MiR-3133 was significantly downregulated in BLM group and upregulated in olmesartan group. Transfection with miR-3133 inhibitor significantly reversed the effects of olmesartan on age-associated migration and invasion of the cells [(85.87±7.39)% vs (49.77±3.05)%; 34.67±2.31 vs 20.00±4.58, P < 0.05] and MMP-2 activation in the cells (1.76±0.19 vs 0.94±0.10, P < 0.05). CONCLUSIONS: Olmesartan inhibits the migration and invasion of ageassociated HA-VSMCs probably by upregulating of the miR-3133 axis.


Asunto(s)
MicroARNs/genética , Músculo Liso Vascular , Movimiento Celular , Proliferación Celular , Células Cultivadas , Humanos , Imidazoles , Metaloproteinasa 2 de la Matriz , Miocitos del Músculo Liso , Tetrazoles
16.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(6): 869-875, 2020 Jun 30.
Artículo en Chino | MEDLINE | ID: mdl-32895200

RESUMEN

OBJECTIVE: To investigate the effect of miR-204 on the invasion and metastasis of breast cancer by targeted regulation of HNRNPA2B1. METHODS: The bioinformatics database was used to obtain data of the expressions of miR-204 in breast cancer patients and the survival rate of the patients. RT-qPCR was used to detect the expression of miR-204 in breast cancer cell lines. The expression vector GV369-miR-204 was used to overexpress miR-204 in MDA-MB-231 cells. Transwell assay was performed to detect the effect of miR-204 on the migration and invasion ability of the breast cancer cells. The key genes (hub genes) of miR-204 were determined by bioinformatics method. A dual luciferase assay was used to analyze the targeting relationship between miR-204 and HNRNPA2B1. The expression of HNRNPA2B1 in MDA-MB-231 cells after miR-204 overexpression was detected by Western blotting, and Transwell assay was used to examine the changes in the cell invasion ability. RESULTS: The expression of miR-204 was decreased in both breast cancer tissues, and was significantly lower in breast cancer MDA-MB-231 cells than in MCF-10A cells (P < 0.05). The decreased expression of miR-204 was associated with poorer prognosis of breast cancer patients (P < 0.05). Upregulation of miR-204 in MDA-MB-231 cells significantly inhibited the invasion and migration of the cells (P < 0.05). Analysis of the data from the Starbase revealed that the expression of miR-204-5p was negatively correlated with the expression of HNRNPA2B1, and the expression of HNRNPA2B1 was increased in breast cancer patients (P < 0.05) in association with a poorer prognosis of the patients (P < 0.05). Dual luciferase assay demonstrated that miR-204 could bind to HNRNPA2B1 in a target-specific manner. Western blotting and Transwell assay showed that miR-204 significant inhibited the migration and invasion ability of breast cancer cells by targeting HNRNPA2B1 (P < 0.05). CONCLUSIONS: miR-204 expression is decreased in breast cancer tissues and cells, and its overexpression can inhibit the invasion and metastasis of breast cancer cells by targeted regulation of HNRNPA2B1.


Asunto(s)
Neoplasias de la Mama , MicroARNs/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Invasividad Neoplásica , Metástasis de la Neoplasia
17.
Medicine (Baltimore) ; 99(37): e21963, 2020 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-32925730

RESUMEN

This study aims to identify differentially expressed microRNAs (miRNAs) in gastric cancer by comparing gastric cancerous tissues with normal tissues, explore the potential roles.The miRNA expression microarray was employed on gastric cancer tissues, and apparently normal para-cancerous tissues from 3 patients undergoing radical surgery were matched. Quantitative RT-PCR was performed on the other 7 patients to validate the findings of the microarray. Furthermore, Gene Ontology (GO) analysis and enrichment analysis of KEGG Pathway were performed for 5 dysregulated candidate miRNAs, including 3 upregulated (miR-31-3p, miR-6736-3p, and miR-147b) and 2 downregulated (miR-3065-5p and miR-3921) miRNAs, in order to determine the role of miRNAs in tumorigenesis and development.Among these miRNAs, 17 miRNAs were found to be upregulated, and 19 miRNAs were found to be downregulated. The dysregulated expression of 5 candidate miRNAs, including miR-31-3p, miR-147b, miR-6736-3p, miR-3065-5p, and miR-3921, were verified by quantitative RT-PCR in the validation set. Among these miRNAs, miR-31-3p, miR-6736-3p, miR-3065-5p, and miR-3921 had 551 target gene intersections. The GO and KEGG Pathway analyses Revealed that miR-31-3p, miR-6736-3p, miR-3065-5p, and miR-3921 may participate in multiple pathophysiological processes, such as foreign substance metabolism and chemical carcinogenesis.The profile of differentially expressed miRNAs was successfully screened, and 4 miRNAs (i.e., miR-31-3p, miR-6736-3p, miR-3065-5p, and miR-3921) appeared to be involved in gastric carcinogenesis. These might serve as promising biomarkers for gastric cancer.


Asunto(s)
Perfilación de la Expresión Génica , MicroARNs/genética , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , Reacción en Cadena en Tiempo Real de la Polimerasa , Regulación hacia Arriba
18.
Medicine (Baltimore) ; 99(37): e22199, 2020 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-32925795

RESUMEN

Colorectal cancer (CRC) is the most common malignant gastrointestinal tumor worldwide. Serum exosomal microRNAs (miRNAs) play a critical role in tumor progression and metastasis. However, the underlying molecular mechanisms are poorly understood.The miRNAs expression profile (GSE39833) was downloaded from Gene Expression Omnibus (GEO) database. GEO2R was applied to screen the differentially expressed miRNAs (DEmiRNAs) between healthy and CRC serum exosome samples. The target genes of DEmiRNAs were predicted by starBase v3.0 online tool. The gene ontology (GO) and Kyoto Encyclopedia of Genomes pathway (KEGG) enrichment analysis were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool. The protein-protein interaction (PPI) network was established by the Search Tool for the Retrieval of Interacting Genes (STRING) visualized using Cytoscape software. Molecular Complex Detection (MCODE) and cytohubba plug-in were used to screen hub genes and gene modules.In total, 102 DEmiRNAs were identified including 67 upregulated and 35 downregulated DEmiRNAs, and 1437 target genes were predicted. GO analysis showed target genes of upregulated DEmiRNAs were significantly enriched in transcription regulation, protein binding, and ubiquitin protein ligase activity. While the target genes of downregulated DEmiRNAs were mainly involved in transcription from RNA polymerase II promoter, SMAD binding, and DNA binding. The KEGG pathway enrichment analyses showed target genes of upregulated DEmiRNAs were significantly enriched in proteoglycans in cancer, microRNAs in cancer, and phosphatidylinositol-3 kinases/Akt (PI3K-Akt) signaling pathway, while target genes of downregulated DEmiRNAs were mainly enriched in transforming growth factor-beta (TGF-beta) signaling pathway and proteoglycans in cancer. The genes of the top 3 modules were mainly enriched in ubiquitin mediated proteolysis, spliceosome, and mRNA surveillance pathway. According to the cytohubba plugin, 37 hub genes were selected, and 4 hub genes including phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), SRC, cell division cycle 42 (CDC42), E1A binding protein p300 (EP300) were identified by combining 8 ranked methods of cytohubba.The study provides a comprehensive analysis of exosomal DEmiRNAs and target genes regulatory network in CRC, which can better understand the roles of exosomal miRNAs in the development of CRC. However, these findings require further experimental validation in future studies.


Asunto(s)
Neoplasias Colorrectales/genética , Biología Computacional/métodos , MicroARNs/genética , Bases de Datos Genéticas , Perfilación de la Expresión Génica , Genes Relacionados con las Neoplasias , Humanos , Análisis por Matrices de Proteínas , Mapas de Interacción de Proteínas
19.
Nat Commun ; 11(1): 4641, 2020 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-32934213

RESUMEN

Despite recent advances in circuit engineering, the design of genetic networks in mammalian cells is still painstakingly slow and fraught with inexplicable failures. Here, we demonstrate that transiently expressed genes in mammalian cells compete for limited transcriptional and translational resources. This competition results in the coupling of otherwise independent exogenous and endogenous genes, creating a divergence between intended and actual function. Guided by a resource-aware mathematical model, we identify and engineer natural and synthetic miRNA-based incoherent feedforward loop (iFFL) circuits that mitigate gene expression burden. The implementation of these circuits features the use of endogenous miRNAs as elementary components of the engineered iFFL device, a versatile hybrid design that allows burden mitigation to be achieved across different cell-lines with minimal resource requirements. This study establishes the foundations for context-aware prediction and improvement of in vivo synthetic circuit performance, paving the way towards more rational synthetic construct design in mammalian cells.


Asunto(s)
Expresión Génica , Mamíferos/genética , MicroARNs/genética , Animales , Redes Reguladoras de Genes , Humanos , Mamíferos/metabolismo , Proteínas/genética , Proteínas/metabolismo
20.
Medicine (Baltimore) ; 99(38): e22261, 2020 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-32957376

RESUMEN

Pancreatic cancer (PC) is one of the major causes of cancer mortality in developed countries. Therefore, there is an urgent need to derive biomarkers for early diagnosis of PC patients at high risk.This study was designed to identify a panel of miRNAs that might serve as biomarkers for the early diagnosis of PC.The data containing both PC and control samples were extracted from the Gene Expression Omnibus (GEO) database. EdgeR was applied to identify the differentially expressed miRNAs and genes between PC patients and healthy controls. Then a miRNA-mRNA network was constructed based on the differentially expressed miRNAs and genes. The miRNAs-based biomarker for PC was finally constructed by random forest. Finally, AUC was used to evaluate the performance of miRNAs to classify PC and control samples.A total of 33 differentially expressed miRNAs, 753 differentially expressed genes, and 8 miRNAs (hsa-mir-139, hsa-mir-31, hsa-mir-196b, hsa-mir-221, hsa-mir-203b, hsa-mir-215, hsa-mir-144, and hsa-mir-4433b) that play important roles in PC were identified. The target genes of these miRNAs were found to be mainly enriched in negative regulation of acute inflammatory response cell-substrate responses, and o-glycan processing pathways. The constructed biomarkers based on these 8 miRNAs could distinguish samples coming from PC and healthy controls.We identified a panel of eight-miRNAs that would serve as early diagnostic biomarkers for PC patients.


Asunto(s)
Biomarcadores de Tumor/genética , Detección Precoz del Cáncer , MicroARNs/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Perfilación de la Expresión Génica , Humanos , Pronóstico , ARN Mensajero/genética
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