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1.
BMC cancer ; 21(1): 575-678, May., 2021. ilus., graf., tab.
Artigo em Inglês | Sec. Est. Saúde SP, CONASS, SESSP-IDPCPROD, Sec. Est. Saúde SP | ID: biblio-1224518

RESUMO

BACKGROUND: No biomarker is available for identifying cancer patients at risk of developing nephrotoxicity when treated with cisplatin. METHODS: We performed microRNA (miRNA) sequencing using plasma collected 5 days after cisplatin treatment (D5) from twelve patients with head and neck cancer with and without nephrotoxicity (grade ≥ 2 increased serum creatinine). The most differentially expressed miRNAs between the two groups were selected for quantification at baseline and D5 in a larger cohort of patients. The association between miRNAs and nephrotoxicity was evaluated by calculating the odds ratio (OR) from univariate logistic regression. Receiver operating characteristic curves (ROC) were used to estimate the area under the curve (AUC), sensitivity, and specificity. RESULTS: MiR-3168 (p = 1.98 × 10− 8 ), miR-4718 (p = 4.24 × 10− 5 ), and miR-6125 (p = 6.60 × 10− 5 ) were the most differentially expressed miRNAs and were further quantified in 43, 48, and 53 patients, respectively. The baseline expression of miR-3168 (p = 0.0456, OR = 1.03, 95% CI: 1.00­1.06) and miR-4718 (p = 0.0388, OR = 1.56, 95% CI: 1.03­ 2.46) were associated with an increased risk of nephrotoxicity, whereas miR-6125 showed a trend (p = 0.0618, OR = 1.73, 95% CI: 0.98­3.29). MiR-4718 showed the highest AUC (0.77, 95% CI: 0.61­0.93) with sensitivity of 66.76 and specificity of 79.49. CONCLUSIONS: We have provided evidence of baseline plasmatic expression of miR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity.


Assuntos
Cisplatino , MicroRNAs , Nefropatias , Neoplasias
2.
Ceska Gynekol ; 86(3): 220-234, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34192880

RESUMO

BACKGROUND: Radiation therapy plays a leading role in the treatment of prostate cancer, but the emergence of radioresistant forms of this disease dictates the need for a personalized ap-proach based on the data from genetic and epigenetic markers. Such markers include the copy number variation as well as gene and microRNA expression. PURPOSE: The aim of the study was to validate the list of potential predictors of radioresistance of prostate tumor cells in a model experiment based on the determination of gene copy number variation, gene transcriptional activity and microRNA expression. MATERIAL AND METHODS: The study used a PC-3 prostate cancer cell culture. The determination of the relative copy number variation and expression of 32 genes (BRCA1, BRCA2, PTEN, CASP3, CASP8, BAX, BCL2, CASP9, P53, MDM2, AKT1, ATM, BRIP1, CDK1, CDKN1B, CCND1, CCND3, FGFR2, KU70, RAD50, RAP80, Rif1, RNF168, TopBP1, HIST, H2AX, EXO1, XRCC4, RBBP8, EP300, LIG4, C-FLIP), as well as 15 microRNAs (let-7, miR15a/ 16, miR-17, miR-18a, miR-21, miR-24, miR-26b, miR-99a, miR-100, miR-101, miR-106a, miR-663a, miR-143, miR-145) was performed using the real-time quantitative polymerase chain reaction method. It was found that daily irradiation of PC-3 cells on a Novalis TX linear accelerator at doses of 6 and 7 Gy for 5 days leads to a significant decrease in the total number of cells and the number of viable cells. Nevertheless, after 5 days of irradiation, about 15% of the initial number of prostate tumor cells retained their viability, which is due to their special genetic and epigenetic characteristics: increased copy number and expression of genes BRCA2, CDK1, CDKN1B, H2AX, RAD50, XRCC4, RBBP8 and EP300 and reduced copy number and expression of CCND3, TP53, and BCL2 genes, as well as differential expression of six microRNAs (hsa-miR-18a-5p, hsa-miR-24-5p, hsa-miR-99a-5p, hsa-miR-100-5p, hsa-miR-145-5p, hsa-let-7a-3p). CONCLUSION: This study enabled to identify genetic and epigenetic markers of prostate tumor cells resistance to radiation therapy.


Assuntos
MicroRNAs , Neoplasias da Próstata , Variações do Número de Cópias de DNA , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Neoplasias da Próstata/genética
3.
Talanta ; 233: 122600, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215088

RESUMO

Selective and sensitive detection of microRNA is crucial for early diagnosis and pathogenesis of disease. Here, we established a novel electrochemical biosensor for simple and accurate analysis of the tumor biomarker microRNA-141, which was based on in-situ catalytic hairpin assembly (CHA) actuated DNA tetrahedral (DTN) interfacial probes. Two hairpin structures used for CHA reaction were placed on the DTN, in which the hairpin H1 on the one vertex of DTN and hairpin H2 embedded in adjacent edge, respective. The target microRNA-141 could open the hairpin H1 and activated the in-situ CHA reaction between H1 and H2 to alter the conformational of DTN, increasing the chances of the direct interaction between methylene blue (MB) and the electrode surface, leading to an increase in the electrochemical signal. Meanwhile, the released miRNA-141 could unfold another H1, enabling the enzyme-free recycling of the target to obtain amplified electrochemical signals. Moreover, the in-situ catalytic hairpin assembly reaction on DTN could shorten the reaction time and enhance the sensitivity. The established biosensor exhibited a wide linear dynamic range of miRNA-141 from 1 fM to 100 pM with a detection limit of 0.32 fM. Besides, the approach can discriminate the target miRNA from mismatched ones with excellent selectivity and can be successfully applied in diluted serum samples, holding great potential for sensitive detection of various biomarkers clinically.


Assuntos
Técnicas Biossensoriais , DNA Catalítico , MicroRNAs , Sondas de DNA/genética , Técnicas Eletroquímicas , Limite de Detecção , MicroRNAs/genética
4.
Talanta ; 233: 122517, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215132

RESUMO

On-chip microparticle-based separation is a significant activity in analytical and biomedical field. Here, we reported an acoustic aggregation-induced microparticle separation for on-chip fluorescence detection of Alzheimer biomarkers. miRNA-101, an Alzheimer-related biomarker, was used as a model target to validate the performance of the acoustic aggregation-induced separation assay. Under the ultrasound filed, the microparticles would move toward the centre of chip by simply adjusting the frequency and voltage. Such particle aggregation further resulted in fluorescence enhancement comparing with single microparticle. This approach integrated acoustic aggregation-induced microparticle separation with fluorescence enhancement, holding great potential application for the development of lab-on-a-chip based trace biomarkers detection in diagnosis field.


Assuntos
Doença de Alzheimer , MicroRNAs , Acústica , Doença de Alzheimer/diagnóstico por imagem , Biomarcadores , Fluorescência , Humanos , Dispositivos Lab-On-A-Chip
5.
Talanta ; 233: 122518, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34215133

RESUMO

MicroRNAs (miRNAs) play an important role in multiple biological processes and can be used as biomarkers for clinical disease diagnosis, so their detection is of great importance. Here, manganese dioxide (MnO2) nanosheet acts as carrier to deliver DNAzyme probes into cells through endocytosis, where intracellular glutathione (GSH) reduces the MnO2 nanosheet to manganese ions (Mn2+) and releases the probes. The generated Mn2+ can be further used as an effective cofactor to activate the DNAzyme probe, and cleave the DNA strand into two fragments. Then, the miRNA-155 in the cells can hybridize with the cleaved fragment to cause the fluorescence signal change of the probe. The proposed proportional fluorescent method has been applied to the imaging of miRNA-155 in HeLa cells and HepG2 cells with the estimated detection limit (LOD) as 1.6 × 10-12 M. The new method can provide great help for cancer diagnosis and biological research related to miRNA.


Assuntos
DNA Catalítico , MicroRNAs , DNA Catalítico/genética , Corantes Fluorescentes , Células HeLa , Humanos , Compostos de Manganês , MicroRNAs/genética , Óxidos
6.
World J Surg Oncol ; 19(1): 199, 2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-34218800

RESUMO

BACKGROUND: Dysregulation of long non-coding RNAs has been implied to connect with cancer progression. This research was to decipher the mechanism of long non-coding RNA SDCBP2-AS1 in ovarian cancer (OC) through regulation of microRNA (miR)-100-5p and ependymin-related protein 1 (EPDR1). METHODS: LncRNA SDCBP2-AS1 and EPDR1 levels in OC were assessed by Gene Expression Profiling Interactive Analysis. lncRNA SDCBP2-AS1, miR-100-5p, and EPDR1 levels in OC tissues and cells were determined. SKOV3 and A2780 cells were transfected with lncRNA SDCBP2-AS1, miR-100-5p, and EPDR1-related plasmids or sequences, and then their functions in cell viability, apoptosis, migration, and invasion were evaluated. The interplay of lncRNA SDCBP2-AS1, miR-100-5p, and EPDR1 was clarified. RESULTS: LncRNA SDCBP2-AS1 and EPDR1 levels were suppressed whilst miR-100-5p level was elevated in OC. After upregulating lncRNA SDCBP2-AS1 or EPDR1, viability, migration, and invasion of OC cells were impaired, and apoptosis rate was increased. Downregulating EPDR1 or upregulating miR-100-5p partially mitigated upregulated lncRNA SDCBP2-AS1-induced impacts on the biological functions of OC cells. LncRNA SDCBP2-AS1 sponged miR-100-5p, and EPDR1 was targeted by miR-100-5p. CONCLUSION: It is illustrated that lncRNA SDCBP2-AS1 regulates EPDR1 by sponge adsorption of miR-100-5p to inhibit the progression of OC.


Assuntos
MicroRNAs , Neoplasias Ovarianas , RNA Longo não Codificante , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas de Neoplasias , Proteínas do Tecido Nervoso , Neoplasias Ovarianas/genética , Prognóstico
7.
Zhonghua Gan Zang Bing Za Zhi ; 29(6): 571-574, 2021 Jun 20.
Artigo em Chinês | MEDLINE | ID: mdl-34225433

RESUMO

Objective: To investigate the expression of miR-495 and its effect on MHCC-97H hepatocellular carcinoma cells. Methods: Fifty-six hepatocellular carcinoma tissue specimens (HCC group) and 40 normal liver tissue specimens (control group) preserved in our hospital from January 2017 to January 2018 were selected. Reverse transcription real-time fluorescent quantitative PCR (qRT-PCR) was used for miR-495 expression detection. MHCC-97H HCC cells were randomly selected and then divide into control group, blank plasmid group and transfection group. The blank plasmid group was transfected with blank plasmid, and the transfection group was transfected with miR-495 inhibitor. The expression of miR-495 in each group of cells were detected using qRT-PCR. CCK method was used to detect each group proliferation activity. Transwell cell migration assay was used to detect each group migration ability. Analysis of variance was used for comparison between multiple groups. Furthermore, LDS-t test was used for pairwise comparison, and t -test was used for comparison between the two groups. Results: The relative expression levels of miR-495 in the HCC group was (2.043 ± 0.382), which was higher than the control group, and the difference between the two groups was statistically significant (P < 0.05). The relative expressions levels of miR-495 in patients with stage III to IV and lymph node metastasis were 2.265 ± 0.284 and 2.290 ± 0.355, which were significantly higher than those of stage I to II and no lymph node metastasis (P < 0.05). The relative expression levels of miR-495 in transfection group was 0.653 ± 0.102, which were significantly lower than control group and blank plasmid group (P < 0.05). The A values of MHCC-97H cells cultured for 24 h and 48 h in transfection group were 0.404 ± 0.106 and 0.604 ± 0.136, which were significantly lower than control group and blank plasmid group (P < 0.05). MHCC-97H cells migration number in the transfection group was (6.10 0 ± 20), which was significantly lower than that of control group and blank plasmid group (P < 0.05). Conclusion: miR-495 high expression has certain relationship with clinicopathological characteristics of HCC tissues. In addition, miR-495 has a certain effect on the proliferation and migration ability of MHCC-97H HCC cells.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , MicroRNAs/genética
8.
Planta ; 254(2): 25, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226949

RESUMO

MAIN CONCLUSION: Some salt-stress responsive DEGs, mainly involved in ion transmembrane transport, hormone regulation, antioxidant system, osmotic regulation, and some miRNA jointly regulated the salt response process in allotriploid Populus cathayana. The molecular mechanism of plant polyploid stress resistance has been a hot topic in biological research. In this study, Populus diploids and first division restitution (FDR) and second division restitution (SDR) triploids were selected as research materials. All materials were treated with 70 mM NaCl solutions for 30 days in the same pot environment. We observed the growth state of triploids and diploids and determined the ratio of potassium and sodium ions, peroxidase (POD) activity, proline content, and ABA and jasmonic acid (JA) hormone content in leaves in the same culture environment with the same concentration of NaCl solution treatment. In addition, RNA-seq technology was used to study the differential expression of mRNA and miRNA. The results showed that triploid Populus grew well and the K+ content and the K+/Na+ ratio in the salt treatment were significantly lower than those in the control. The contents of ABA, JA, POD, and proline were increased compared with contents in diploid under salt stress. The salt-stress responsive DEGs were mainly involved in ion transport, cell homeostasis, the MAPK signaling pathway, peroxisome, citric acid cycle, and other salt response and growth pathways. The transcription factors mainly included NAC, MYB, MYB_related and AP2/ERF. Moreover, the differentially expressed miRNAs involved 32 families, including 743 miRNAs related to predicted target genes, among which 22 miRNAs were significantly correlated with salt-stress response genes and related to the regulation of hormones, ion transport, reactive oxygen species (ROS) and other biological processes. Our results provided insights into the physiological and molecular aspects for further research into the response mechanisms of allotriploid Populus cathayana to salt stress. This study provided valuable information for the salt tolerance mechanism of allopolyploids.


Assuntos
MicroRNAs , Populus , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , MicroRNAs/genética , Populus/genética , Tolerância ao Sal/genética , Transcriptoma
9.
Front Immunol ; 12: 685344, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211472

RESUMO

Vaccination is the best prophylaxis for the prevention of infectious diseases, including coronavirus disease 2019. However, the efficacy of vaccines and onset of adverse reactions vary among individuals. Circulating extracellular vesicles (EVs) regulate the immune responses after vaccination by delivering microRNAs (miRNAs) to myeloid and lymphoid cells. Among these, miR-192 levels in serum EVs increase with aging, in an IL-6-dependent manner, reducing excessive IL-6 expression in aged mice, creating a negative feedback loop. Excessive IL-6 expression reduces vaccination efficacy in aged mice, while EV miR-192 improves efficacy in these aged mice as well, making this miRNA an interesting focus of study. miR-21 levels in serum EVs also increase with aging, and regulates the expression of IL-12 required for Th1 responses; therefore, EV miR-21 is expected to regulate vaccine efficacy. miR-451a, another important miRNA, is abundant in serum EVs and controls the expression of cytokines, such as type I interferon and IL-6. However, levels differ among individuals and correlate with local inflammatory symptoms experienced after a seasonal flu vaccination. These findings suggest the importance of EV miRNAs as a tool to improve vaccine efficacy and also as biomarkers to predict the immune response and adverse reactions after vaccinations.


Assuntos
Vesículas Extracelulares/metabolismo , Interferon Tipo I/imunologia , Interleucina-6/imunologia , MicroRNAs/sangue , Envelhecimento/sangue , Envelhecimento/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Humanos , Interferon Tipo I/biossíntese , Subunidade p35 da Interleucina-12/biossíntese , Subunidade p35 da Interleucina-12/imunologia , Interleucina-6/biossíntese , MicroRNAs/genética , SARS-CoV-2/imunologia , Células Th1/imunologia , Vacinação
10.
BMC Gastroenterol ; 21(1): 284, 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34247571

RESUMO

BACKGROUND: Gastrointestinal adenocarcinoma (GIAD) has caused a serious disease burden globally. Targeted therapy for the transforming growth factor beta (TGF-ß) signaling pathway is becoming a reality. However, the molecular characterization of TGF-ß associated signatures in GIAD requires further exploration. METHODS: Multi-omics data were collected from TCGA and GEO database. A pivotal unsupervised clustering for TGF-ß level was performed by distinguish status of TGF-ß associated genes. We analyzed differential mRNAs, miRNAs, proteins gene mutations and copy number variations in both clusters for comparison. Enrichment of pathways and gene sets were identified in each type of GIAD. Then we performed differential mRNA related drug response by collecting data from GDSC. At last, a summarized deep neural network for TGF-ß status and GIADs was constracted. RESULTS: The TGF-ßhigh group had a worse prognosis in overall GIAD patients, and had a worse prognosis trend in gastric cancer and colon cancer specifically. Signatures (including mRNA and proteins) of the TGF-ßhigh group is highly correlated with EMT. According to miRNA analysis, miR-215-3p, miR-378a-5p, and miR-194-3p may block the effect of TGF-ß. Further genomic analysis showed that TGF-ßlow group had more genomic changes in gastric cancer, such as TP53 mutation, EGFR amplification, and SMAD4 deletion. And drug response dataset revealed tumor-sensitive or tumor-resistant drugs corresponding to TGF-ß associated mRNAs. Finally, the DNN model showed an excellent predictive effect in predicting TGF-ß status in different GIAD datasets. CONCLUSIONS: We provide molecular signatures associated with different levels of TGF-ß to deepen the understanding of the role of TGF-ß in GIAD and provide potential drug possibilities for therapeutic targets in different levels of TGF-ß in GIAD.


Assuntos
Adenocarcinoma , MicroRNAs , Preparações Farmacêuticas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Variações do Número de Cópias de DNA , Humanos , MicroRNAs/genética , Fator de Crescimento Transformador beta/genética
11.
Anal Chim Acta ; 1174: 338715, 2021 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-34247740

RESUMO

Circulating microRNAs (miRNAs) have the potential to become reliable and noninvasive biomarkers for ovarian cancer (OC) diagnosis; however, the conventional miRNAs detection techniques exhibit enduring limitations of low sensitivity and specificity. Graphene oxide (GO), a novel nanomaterial, is at the forefront of material design for extensive biomedical applications. Owing to the excellent water affinity and single-stranded DNA (ssDNA) adsorption characteristics of GO, we designed and developed a GO-based qRT-PCR assay for the detection of miRNAs associated with OC. In the GO-based qRT-PCR system, GO could significantly improve the sensitivity and specificity of the qRT-PCR assay by noncovalently interacting with primers and ssDNA and reducing the occurrence of non-specific amplification. Moreover, the detection of miRNAs associated with OC confirmed that GO-based qRT-PCR assay could differentiate benign ovarian tumors from OC (sensitivity, 0.91; specificity, 1.00). Collectively, these findings provide robust evidence that GO-based qRT-PCR assay can be effectively used as a promising method to detect miRNAs for the screening of OC patients.


Assuntos
MicroRNAs , Neoplasias Ovarianas , Detecção Precoce de Câncer , Feminino , Grafite , Humanos , MicroRNAs/genética , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , Reação em Cadeia da Polimerase
12.
Int J Mol Sci ; 22(12)2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198485

RESUMO

Brain microvascular endothelial cells (BMECs) constitute the structural and functional basis for the blood-brain barrier (BBB) and play essential roles in bacterial meningitis. Although the BBB integrity regulation has been under extensive investigation, there is little knowledge regarding the roles of long non-coding RNAs (lncRNAs) in this event. The present study aimed to investigate the roles of one potential lncRNA, lncRSPH9-4, in meningitic E. coli infection of BMECs. LncRSPH9-4 was cytoplasm located and significantly up-regulated in meningitic E. coli-infected hBMECs. Electrical cell-substrate impedance sensing (ECIS) measurement and Western blot assay demonstrated lncRSPH9-4 overexpression in hBMECs mediated the BBB integrity disruption. By RNA-sequencing analysis, 639 mRNAs and 299 miRNAs were significantly differentiated in response to lncRSPH9-4 overexpression. We further found lncRSPH9-4 regulated the permeability in hBMECs by competitively sponging miR-17-5p, thereby increasing MMP3 expression, which targeted the intercellular tight junctions. Here we reported the infection-induced lncRSPH9-4 aggravated disruption of the tight junctions in hBMECs, probably through the miR-17-5p/MMP3 axis. This finding provides new insights into the function of lncRNAs in BBB integrity during meningitic E. coli infection and provides the novel nucleic acid targets for future treatment of bacterial meningitis.


Assuntos
Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Escherichia coli/fisiologia , Metaloproteinase 3 da Matriz/metabolismo , Meningites Bacterianas/genética , Meningites Bacterianas/microbiologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Sequência de Bases , Citoplasma/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais/microbiologia , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , Microvasos/patologia , Modelos Biológicos , Permeabilidade , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais , Junções Íntimas/metabolismo , Transcrição Genética , Regulação para Cima/genética
13.
Biosens Bioelectron ; 190: 113470, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34229191

RESUMO

MicroRNAs (miRNAs) are promising biomarkers for the early diagnosis of breast cancer. Yet, simultaneous achievement of rapid, sensitive and accurate detection of diverse miRNAs in clinical samples is still challenging due to the low abundance of miRNAs and the complex procedures of RNA extraction and separation. Herein, we develop an innovative three-dimensional (3D) surface-enhanced Raman scattering (SERS) holography sensing strategy for rapid, sensitive and multiplexed detection of human breast cancer-associated miRNAs. To establish a proof of concept, nine kinds of human breast cancer-associated miRNAs are isothermally amplified by Exonuclease (Exo) III enzyme, and the products could be spatially separated to corresponding sensing region on silicon SERS substrates. Each region has been modified with corresponding hairpin DNA probes, which are used to identify and quantify the miRNAs. Different DNA probes are labeled with different Raman reporters, which serve as "SERS tags" to incorporate spectroscopic information into computer-generated 3D SERS hologram within ~9 min. We demonstrate that 3D SERS holography chip not only achieves an ultrahigh sensitivity down to ~1 aM but also feature a high correlation with RT-qPCR in the detection of nine miRNAs in 30 clinical serum samples. This work provides a feasible tool to improve the diagnosis of breast cancer.


Assuntos
Técnicas Biossensoriais , Neoplasias da Mama , Holografia , Nanopartículas Metálicas , MicroRNAs , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Feminino , Humanos , MicroRNAs/genética , Análise Espectral Raman
14.
Clinics (Sao Paulo) ; 76: e2669, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34231706

RESUMO

OBJECTIVES: This study aimed to explore the efficacy of combination treatment with dendrobium mixture and metformin (Met) in diabetic cardiomyopathy (DCM) and its effects on NEAT1 and the Nrf2 signaling pathway. METHODS: H9c2 cells were maintained in medium supplemented with either low (5.5 mmol/L) or high (50 mmol/L) glucose. Male Sprague-Dawley rats were fed a high-glucose diet and administered a single, low dose of streptozotocin (35 mg/kg) via intraperitoneal injection to induce the development of DM. After induction of DM, the rats were treated with dendrobium mixture (10 g/kg) and Met (0.18 g/kg) daily for 4 weeks. Next, quantitative reverse transcription (qRT)-PCR and western blotting were performed to evaluate the expression levels of target genes and proteins. Flow cytometry was performed to assess apoptosis, and hematoxylin and eosin staining was performed to evaluate the morphological changes in rat cardiac tissue. RESULTS: In patients with diabetes mellitus (DM) and myocardial cells and heart tissues from rats with high glucose-induced DM, NEAT1 was downregulated, and the expression levels of Nrf2 were decreased (p<0.01, p<0.001). The combination of dendrobium mixture and Met upregulated the expression of NEAT1 which upregulated Nrf2 by targeting miR-23a-3p, resulting in reduced apoptosis and improved cardiac tissue morphology (p<0.01, p<0.001). CONCLUSION: Dendrobium mixture and Met upregulated the expression of NEAT1 in DCM, thereby inhibiting apoptosis of myocardial cells.


Assuntos
Dendrobium , Diabetes Mellitus , Cardiomiopatias Diabéticas , Metformina , MicroRNAs , RNA Longo não Codificante , Animais , Apoptose , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/genética , Humanos , Masculino , RNA Longo não Codificante/genética , Ratos , Ratos Sprague-Dawley
15.
J Agric Food Chem ; 69(28): 8038-8049, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34236846

RESUMO

Appropriately increasing intramuscular fat content can help improve meat quality, so it is necessary to explore the internal molecular mechanism of preadipocyte differentiation. The role of heme oxygenase 1 (HO1) in cell oxidative stress, energy metabolism, cell proliferation, and differentiation has gradually been revealed. Here, we used 3'RACE to identify the full-length 3' untranslated region (3'UTR) of HO1 and found that a very short 3'UTR variant was produced by alternative polyadenylation (APA). HO1 with a long 3'UTR variant was identified as a direct target of miR155-5P and miR377-3P. Our experimental results verified the inhibitory effect of HO1 on preadipocyte differentiation. In addition, our research confirms that by escaping microRNA inhibitory effects, the HO1 3'UTR short variant produced by APA has a higher level of expression. Thus, the HO1 3'UTR short variant has a stronger inhibitory effect on the preadipocyte differentiation than the HO1 3'UTR long variants in 3T3-L1.


Assuntos
MicroRNAs , Poliadenilação , Regiões 3' não Traduzidas , Células 3T3-L1 , Adipogenia/genética , Animais , Heme Oxigenase-1/genética , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo
16.
Science ; 373(6551)2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244384

RESUMO

Children with Down syndrome have a 150-fold increased risk of developing myeloid leukemia, but the mechanism of predisposition is unclear. Because Down syndrome leukemogenesis initiates during fetal development, we characterized the cellular and developmental context of preleukemic initiation and leukemic progression using gene editing in human disomic and trisomic fetal hematopoietic cells and xenotransplantation. GATA binding protein 1 (GATA1) mutations caused transient preleukemia when introduced into trisomy 21 long-term hematopoietic stem cells, where a subset of chromosome 21 microRNAs affected predisposition to preleukemia. By contrast, progression to leukemia was independent of trisomy 21 and originated in various stem and progenitor cells through additional mutations in cohesin genes. CD117+/KIT proto-oncogene (KIT) cells mediated the propagation of preleukemia and leukemia, and KIT inhibition targeted preleukemic stem cells.


Assuntos
Proteínas de Ciclo Celular/genética , Síndrome de Down/genética , Fator de Transcrição GATA1/genética , Células-Tronco Hematopoéticas/fisiologia , Leucemia Mieloide/genética , Pré-Leucemia/genética , Animais , Antígenos CD34/análise , Proteínas de Ciclo Celular/metabolismo , Linhagem da Célula , Proliferação de Células , Transformação Celular Neoplásica , Proteínas Cromossômicas não Histona/genética , Cromossomos Humanos Par 21/genética , Cromossomos Humanos Par 21/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Síndrome de Down/complicações , Feminino , Fator de Transcrição GATA1/metabolismo , Hematopoese , Transplante de Células-Tronco Hematopoéticas , Xenoenxertos , Humanos , Leucemia Mieloide/metabolismo , Leucemia Mieloide/patologia , Fígado/embriologia , Masculino , Megacariócitos/fisiologia , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Mutação , Pré-Leucemia/metabolismo , Pré-Leucemia/patologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-kit/análise , Proteínas Proto-Oncogênicas c-kit/antagonistas & inibidores
18.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(7): 730-734, 2021 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-34266532

RESUMO

OBJECTIVE: To determine the association of circular RNA (circRNA) and circRNA-microRNA (miRNA) network regulation with brain injury induced by inflammation in preterm mice. METHODS: Pregnant mice were treated with intraperitoneally injected lipopolysaccharide to establish a preterm mouse model of brain injury induced by inflammation (inflammation preterm group with 3 mice). Preterm mice born to normal pregnant mice by cesarean section were selected as controls (non-inflammation preterm group with 3 mice). The gene microarray technique was used to screen out the circRNAs associated with brain injury in preterm mice. The miRNA target prediction software was used to predict the binding sites between circRNAs and miRNAs and analyze the regulatory mechanism. RESULTS: A total of 365 differentially expressed circRNAs were screened out between the inflammation preterm and non-inflammation preterm groups (fold change > 1.5, P < 0.05), among which there were 206 upregulated circRNAs and 159 downregulated circRNAs. Further analysis of the circRNAs with a fold change of > 4 showed that these circRNAs could bind to miRNAs and regulate their activity, thereby regulating the expression of the genes associated with the nervous system. CONCLUSIONS: Inflammation induces a significant change in the expression profile of circRNAs in the brain tissue of mice, and the change in the expression of circRNAs plays an important role in brain injury induced by inflammation and subsequent brain development in preterm mice.


Assuntos
Lesões Encefálicas , MicroRNAs , Animais , Cesárea , Feminino , Perfilação da Expressão Gênica , Inflamação/genética , Camundongos , MicroRNAs/genética , Gravidez , RNA/genética , RNA Circular
19.
Planta ; 254(2): 31, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34283297

RESUMO

MAIN CONCLUSION: Comparative analysis of miRNAs and their gene targets between the evergreen and yellowish-brown Cryptomeria fortunei phenotypes in cold winters suggests a possible role of miRNA-regulated pathways in needle color. Cryptomeria fortunei (Chinese cedar) is a conifer tree of considerable economic, ornamental and ecological importance. Despite the evergreen nature of C. fortunei, most needles turn yellowish- or reddish-brown in winter. The roles of microRNAs (miRNAs) in regulating pigment biosynthesis in color-leafed plants have been widely investigated. However, whether or not an miRNA-mediated staged discoloration mechanism exists in evergreen C. fortunei is currently unknown. In this study, we deciphered the microRNAs landscape in overwintering C. fortunei needles using high-throughput sequencing. A total of 517 known and 212 novel miRNA mature/star sequences, including 233 differentially expressed miRNAs, were identified. Based on integrated transcriptome and miRNA analysis, 2702 target unigenes of the miRNAs were predicted and these targets were significantly enriched in pigment-related biosynthesis pathways. A miRNA-target pigment biosynthesis regulatory network was then constructed, and its module miRNA (ath-miR858b, aly-miR858-3p, cme-miR828 and novel33_mature)-MYBs (v-myb avian myeloblastosis viral oncogene homolog) appeared to be a key factor regulating needle discoloration in C. fortunei. These miRNA-MYBs were further confirmed by degradome sequencing. Overall, these findings provide new insight into the posttranscriptional regulatory mechanism of leaf/needle discoloration in gymnosperms and may contribute to the miRNA-mediated genetic improvement of evergreen C. fortunei needles.


Assuntos
Cryptomeria , MicroRNAs , China , Regulação da Expressão Gênica de Plantas , Sequenciamento de Nucleotídeos em Larga Escala , MicroRNAs/genética , Agulhas , RNA de Plantas/genética , Árvores/genética
20.
Yi Chuan ; 43(7): 680-693, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34284983

RESUMO

The number of Sertoli cells in the testis is a major regulator on the sperm production capacity. MicroRNAs (miRNAs) participate in regulating the proliferation and apoptosis of porcine immature Sertoli cells. However, the functions and mechanisms of action of most identified miRNAs in porcine Sertoli cells remain largely unknown. In the present study, based on our previous results from an EdU-based high-content screening assay, we further studied the mechanism of action of miR-191 on the proliferation and apoptosis of porcine immature Sertoli cells through flow cytometry, Western blotting, and dual-luciferase activity analyses. The results demonstrated that overexpression of miR-191 promoted cell cycle progression from G1 phase to the S and G2 phases, enhanced cell proliferation, and inhibited apoptosis in the porcine immature Sertoli cells, whereasmiR-191 inhibition resulted in the opposite effects. The results from a luciferase reporter assay showed that miR-191 directly targeted the 3'-UTR of theBDNF gene. BDNF knockdown also promoted cell cycle progression to the S phase, cell proliferation and inhibited cell apoptosis, which were consistent with the effects of the miR-191overexpression. A co-transfection experiment showed that BDNF knockdown abolished the effects of miR-191 inhibition. Furthermore, both miR-191 overexpression and BDNFinhibition elevated the phosphorylation of PI3K and AKT, the key components of the PI3K/AKT signaling pathway, whereas BDNFinhibition offset the effects of the miR-191 knockdown. Overall, these data indicated that miR-191 promotes cell proliferation and inhibits apoptosis in porcine immature Sertoli cells by targeting theBDNF gene through activating the PI3K/AKT signaling pathway. This study provides a novel scientific basis for further investigation on the biological functions of miR-191 on porcine spermatogenesis.


Assuntos
MicroRNAs , Fosfatidilinositol 3-Quinases , Animais , Apoptose/genética , Fator Neurotrófico Derivado do Encéfalo/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Masculino , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Suínos
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