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1.
Int J Mol Sci ; 22(10)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-34065034

RESUMO

Seed germination is a key step in the new life cycle of plants. In agriculture, we regard the rapid and consistent process of seed germination as one of the necessary conditions to measure the high quality and yield of crops. ENO2 is a key enzyme in glycolysis, which also plays an important role in plant growth and abiotic stress responses. In our study, we found that the time of seed germination in AtENO2 mutation (eno2-) was earlier than that of wild type (WT) in Arabidopsis thaliana. Previous studies have shown that microRNAs (miRNAs) were vital in seed germination. After deep sequencing of small RNA, we found 590 differentially expressed miRNAs in total, of which 87 were significantly differentially expressed miRNAs. By predicting the target genes of miRNAs and analyzing the GO annotation, we have counted 18 genes related to seed germination, including ARF family, TIR1, INVC, RR19, TUDOR2, GA3OX2, PXMT1, and TGA1. MiR9736-z, miR5059-z, ath-miR167a-5p, ath-miR167b, ath-miR5665, ath-miR866-3p, miR10186-z, miR8165-z, ath-miR857, ath-miR399b, ath-miR399c-3p, miR399-y, miR163-z, ath-miR393a-5p, and ath-miR393b-5p are the key miRNAs regulating seed germination-related genes. Through KEGG enrichment analysis, we found that phytohormone signal transduction pathways were significantly enriched, and these miRNAs mentioned above also participate in the regulation of the genes in plant hormone signal transduction pathways, thus affecting the synthesis of plant hormones and further affecting the process of seed germination. This study laid the foundation for further exploration of the AtENO2 regulation for seed germination.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/fisiologia , Redes Reguladoras de Genes , Germinação , RNA de Plantas/genética , Pequeno RNA não Traduzido/genética , Sementes/fisiologia , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Sequenciamento de Nucleotídeos em Larga Escala , MicroRNAs/genética , Sementes/genética
2.
World J Surg Oncol ; 19(1): 161, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34082777

RESUMO

BACKGROUND: Breast cancer (BC) is the most commonly malignant tumor among women worldwide. Many studies have reported that circular RNAs (circRNAs) were participated in the regulation of multiple cancers development. However, the mechanism underlying hsa_circ_0001982 in breast cancer development is still unclear. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the levels of circ_0001982, microRNA-1287-5p (miR-1287-5p), and mucin 19 (MUC19) in BC tissues and cells under hypoxia. Moreover, glycolysis was evaluated by glucose consumption, lactic acid production, and hexokinase II (HK2) protein levels. The protein levels of cyclin D1, proliferating cell nuclear antigen (PCNA), and HK2 were determined by western blot assay. Cell proliferation, migration, and invasion were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-h-tetrazolium bromide (MTT) and transwell assays, respectively. The relationship between miR-1287-5p and circ_0001982 or MUC19 was predicted using starbase v3.0 or Targetscan, and verified by dual-luciferase reporter assay and RNA binding protein immunoprecipitation (RIP) assay. The xenograft model in nude mice was established to examine the effect of circ_0001982 in vivo. RESULTS: The levels of circ_0001982 and MUC19 were upregulated, while miR-1287-5p was downregulated in BC tissues and cells under hypoxia. Knockdown of circ_0001982 hindered glycolysis, cell viability, migration, and invasion of BC cells under hypoxia. Mechanistic studies discovered that circ_0001982 could act as a sponge for miR-1287-5p to enhance MUC19 expression in BC cells. In addition, circ_0001982 silencing reduced xenograft tumor growth by regulating miR-1287-5p/MUC19 axis. CONCLUSION: Circ_0001982 affected BC cells glycolysis, proliferation, migration, and invasion through miR-1287-5p/MUC19 axis under hypoxia.


Assuntos
Neoplasias da Mama/genética , Hipóxia , MicroRNAs , Mucinas/genética , RNA Circular/genética , Animais , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Hipóxia/genética , Camundongos , Camundongos Nus , MicroRNAs/genética , Transplante de Neoplasias , Prognóstico
3.
BMC Res Notes ; 14(1): 222, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34082815

RESUMO

OBJECTIVE: The impact of psychosocial stress on a variety of negative health outcomes is well documented, with current research efforts directed at possible mechanisms. Here, we focused on a potential mechanism involving differential expression of mRNA and microRNA in response to acute psychosocial stress. We utilized a validated behavioral paradigm, the Trier Social Stress Test (TSST), to induce acute psychosocial stress in a cohort of volunteers. Stress reactivity was assessed repeatedly during the TSST using saliva samples that were analyzed for levels of cortisol. Peripheral blood mononuclear cells were extracted from blood drawn at baseline and at two time points following the stress paradigm. Total RNA was extracted, and mRNA and microRNA microarrays were utilized to assess within-subject changes in gene expression between baseline and the two post-stressor time points. RESULTS: For microarray gene expression analysis, we focused on 12 participants who showed a robust cortisol response to the task, as an indicator of robust HPA-axis activation. We discovered a set of mRNAs and miRNAs that exhibited dynamic expression change in response to the TSST in peripheral blood mononuclear cells, further characterizing the link between psychosocial stress and cellular response mechanisms.


Assuntos
MicroRNAs , Estresse Psicológico/genética , Expressão Gênica , Humanos , Hidrocortisona , Leucócitos Mononucleares , MicroRNAs/genética , Projetos Piloto , RNA Mensageiro/genética , Saliva
4.
World J Surg Oncol ; 19(1): 165, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090463

RESUMO

BACKGROUND: X inactivation-specific transcript (XIST) is the long non-coding RNA (lncRNA) related to cancer, which is involved in the development and progression of various types of tumor. However, up to now, the exact role and molecular mechanism of XIST in the progression of ovarian cancer are not clear. We studied the function of XIST in ovarian cancer cells and clinical tumor specimens. METHODS: RT-qPCR was performed to detect the expression levels of miR-335 and BCL2L2 in ovarian cancer cells and tissues. MTT and transwell assays were carried out to detect cell proliferation, migration, and invasion abilities. Western blot was performed to analyze the expression level of BCL2L2. The interaction between miR-335 and XIST/BCL2L2 was confirmed using a luciferase reporter assay. RESULTS: The inhibition of XIST can inhibit the proliferation invasion and migration of human ovarian cancer cells. In addition, the miR-335/BCL2L2 axis was involved in the functions of XIST in ovarian cancer cells. These results suggested that XIST could regulate tumor proliferation and invasion and migration via modulating miR-335/BCL2L2. CONCLUSION: XIST might be a carcinogenic lncRNA in ovarian cancer by regulating miR-335, and it can serve as a therapeutic target in human ovarian cancer.


Assuntos
MicroRNAs , Neoplasias Ovarianas , RNA Longo não Codificante , Proteínas Reguladoras de Apoptose , Carcinoma Epitelial do Ovário , Feminino , Humanos , MicroRNAs/genética , Neoplasias Ovarianas/genética , Prognóstico , RNA Longo não Codificante/genética
5.
World J Surg Oncol ; 19(1): 163, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090483

RESUMO

BACKGROUND: The incidence of gallbladder carcinoma (GBM) in China has increased in recent years. Here, the functional mechanism of lncRNA TTN-AS1 in GBC was preliminary elucidated. METHODS: The expression levels of lncRNA TTN-AS1, miR-107, and HMGA1 in tissues and cell lines were assessed by RT-qPCR. Cell proliferation was measured by MTT assays. Cell invasion and migration abilities were evaluated by Transwell assays. The relationship between miR-107 and lncRNA TTN-AS1 or HMGA1 was confirmed by luciferase reporter assay. RESULTS: Upregulation of lncRNA TTN-AS1 and downregulation of miR-107 were detected in GBC. Furthermore, the expressions between TTN-AS1 and miR-107 were mutually inhibited in GBC. Functionally, lncRNA TTN-AS1 promoted cell viability and motility in GBC by sponging miR-107. In addition, miR-107 directly targets HMGA1. And HMGA1 can be positively regulated by lncRNA TTN-AS1 in GBC. Furthermore, HMGA1 promoted GBC progression by interacting with lncRNA TTN-AS1/miR-107 axis. CONCLUSION: LncRNA TTN-AS1 acted as a tumor promoter in GBC by sponging miR-107 and upregulating HMGA1.


Assuntos
Neoplasias da Vesícula Biliar , MicroRNAs , RNA Longo não Codificante , Carcinógenos , Linhagem Celular Tumoral , China , Neoplasias da Vesícula Biliar/genética , Regulação Neoplásica da Expressão Gênica , Proteína HMGA1a/genética , Humanos , MicroRNAs/genética , Prognóstico , RNA Longo não Codificante/genética
6.
J Int Med Res ; 49(6): 3000605211016209, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34098766

RESUMO

OBJECTIVE: To explore the role of miR-223 and miR-126 in predicting treatment responses to dual antiplatelet therapy (DAPT) in patients with ST-elevation myocardial infarction (STEMI). METHODS: Plasma miR-223 and miR-126 levels were measured before treatment. Treatment responses and 2-year survival were determined. In vitro experiments were performed to explore the mechanism of action. RESULTS: Patients with resistance to DAPT had a lower level of miR-223 and miR-126. Cardiac-event-free survival was shorter in patients with lower miR-223 or miR-126 levels. MiR-223 and miR-126 independently predicted DAPT resistance. Modulating miR-223 or miR-126 in platelets in vitro significantly changed the response to clopidogrel by regulating platelet aggregation. CONCLUSION: MiR-223 and miR-126 play a role in DAPT resistance and may provide potential biomarkers in patients with STEMI.


Assuntos
MicroRNAs , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Plaquetas , Clopidogrel/uso terapêutico , Humanos , MicroRNAs/genética , Inibidores da Agregação Plaquetária/uso terapêutico , Infarto do Miocárdio com Supradesnível do Segmento ST/tratamento farmacológico , Infarto do Miocárdio com Supradesnível do Segmento ST/genética , Resultado do Tratamento
7.
Gen Physiol Biophys ; 40(3): 207-219, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34100377

RESUMO

Circular RNAs (circRNAs) are related to rheumatoid arthritis (RA) development. However, the function and mechanism of circRNA pituitary tumor-transforming 1 interacting protein (circ- PTTG1IP) in RA are unknown. The expression of circ-PTTG1IP in synovial tissues of RA patients and fibroblast-like synoviocytes from RA patients (RA-FLSs) were detected by RT-qPCR. The results uncovered that circ-PTTG1IP was overexpressed in RA patients and RA-FLSs, and circ-PTTG1IP knockdown suppressed cell proliferation, migration, invasion and inflammatory response in RA-FLSs. Besides, we found that circ-PTTG1IP could directly bind to miR-671-5p, and toll-like receptor 4 (TLR4) was a target of miR-671-5p, which was confirmed by dual-luciferase reporter assay. miR-671-5p inhibitor attenuated the effects of circ-PTTG1IP knockdown on RA-FLSs, while the effects of miR-671-5p mimic on RA-FLSs were partly reversed by TLR4 overexpression. Furthermore, circ-PTTG1IP could upregulate TLR4 expression by miR-671-5p. Thus, circ-PTTG1IP knockdown repressed cell proliferation, migration, invasion and inflammatory response in RA-FLSs by regulating the miR-671-5p/TLR4 axis.


Assuntos
Artrite Reumatoide , MicroRNAs , Sinoviócitos , Apoptose , Artrite Reumatoide/genética , Proliferação de Células , Células Cultivadas , Fibroblastos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , MicroRNAs/genética , Receptor 4 Toll-Like/genética
8.
Gen Physiol Biophys ; 40(3): 235-243, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34100379

RESUMO

We aimed to investigate the effects of puerarin on high glucose (HG)-induced human retinal endothelial cells (HRECs) injury. Cells were exposed to puerarin in the presence or absence of HG challenge. Cell viability was determined using a CCK-8 assay. Then, the levels of the oxidative stress-related factors were evaluated using corresponding kits. Pyroptosis was assessed by measurement of gasdermin-N domain (GSDMD-N) and caspase-1 (CASP1) expression. Subsequently, miR-16-5p expression was detected using RT-qPCR. The levels of oxidative stress and pyroptosis were examined after miR-16-5p silencing. The Starbase database predicted that CASP1 is a potential target of miR-16-5p, which was verified through a luciferase reporter assay. Moreover, CASP1 expression was determined after miR-16-5p silencing in HG-stimulated HRECs with puerarin exposure. Results revealed that puerarin significantly enhanced cell viability and inhibited oxidative stress. Furthermore, puerarin markedly downregulated GSDMD-N and CASP1 expression, and miR-16-5p level was notably inhibited in HG-stimulated HRECs, which was reversed after puerarin intervention. Following transfection with miR-16-5p inhibitor, the effects of puerarin on cell viability, oxidative stress and pyroptosis were attenuated in HG-induced HRECs. CASP1 was confirmed as a direct target gene of miR-16-5p. Taken together, puerarin alleviates oxidative stress and pyroptosis in HG-stimulated HRECs through regulating the miR- 16-5p/CASP1 axis.


Assuntos
Apoptose , MicroRNAs , Caspase 1 , Células Endoteliais , Glucose , Humanos , Isoflavonas , MicroRNAs/genética
9.
Talanta ; 232: 122422, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34074408

RESUMO

Herein, we construct an ingenious spatially localized amplification reaction (SLAR) by colocalizing the entropy-driven reaction (EDR) in a nanometer space, which greatly accelerates target conversion and realizes the sensitive detection of microRNA-21 (miRNA-21). A large number of EDR complex are hybridized with the prefabricated DNA scaffold via a DNA self-assembly strategy to form the SLAR nanoprobe. Target miRNA-21 triggers interval EDR along the long DNA scaffold, resulting in fluorescence recovery with high signal gain because of the fast release of reporter. Compared with reactions with diffusible components, spatial arrangement of all components of EDR on a nanoscale scaffold can increase the local concentration of reactants, accelerating the interaction between adjacent components, and can also avoid the influence of stochastic diffusion to reduce the unintentional binding interaction between further separated components. Therefore, this SLAR assay displayed an excellent analytical performance for miRNA-21 detection with a detection limit of 6 pM and showed good specificity in distinguishing miRNA-21 from similar miRNAs. In addition, the proposed assay has been experimentally demonstrated for estimation of miRNA-21 in MCF-7 and HeLa cells lysates, which exhibited great promise in the sensitive detection of biomarkers in early diagnosis.


Assuntos
Técnicas Biossensoriais , MicroRNAs , Bioensaio , DNA , Entropia , Células HeLa , Humanos , Limite de Detecção , Células MCF-7 , MicroRNAs/genética , Técnicas de Amplificação de Ácido Nucleico
10.
J Biomed Nanotechnol ; 17(5): 822-837, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34082869

RESUMO

Tumour-associated macrophages (TAMs) are thought to contribute to oral squamous cell carcinoma (OSCC) initiation and progression. However, the underlying mechanism through which TAMs foster OSCC progression is still unclear. This study intended to determine whether there are exclusively exosomal miRNAs-derived macrophages that are functionally necessary for OSCC progression. The phenotype of TAM recruitment in OSCC tissue samples was assessed, subsequently identifying the influence of M2 macrophages and exosomes derived from M2 macrophages on OSCC proliferation and tumorigenesis in vitro and in vivo. CD68 and CD163, the specific markers of M2 type macrophages, were upregulated in TAMs presented in intra-cancer tissues. M2 macrophages and M2 macrophage-derived exosomes (M2 exos) both can promote OSCC growth and tumorigenicity. An exosomal RNA-seq analysis was conducted to predict regulatory exosomal miRNAs related to OSCC growth, which determined miR-31-5p and LATS2 for subsequent experiments. Mechanistically, miR-31-5p was delivered to recipient OSCC cells through M2 exos and complementary pairing with the large tumor suppressor 2 (LATS2) coding sequence, thus suppressing the expression of LATS2 and inactivation the Hippo signaling pathway to support OSCC growth. Collectively, our findings demonstrate that M2 macrophage-derived exosomal miR- 31-5p can make tumor suppressor LATS2 gene inhibited and facilitate the progression of OSCC via inhibiting the Hippo signaling pathway, which possibly provides new targets for the molecular therapy of OSCC.


Assuntos
Carcinoma de Células Escamosas , MicroRNAs , Neoplasias Bucais , Transdução de Sinais , Carcinogênese/genética , Carcinoma de Células Escamosas/genética , Proliferação de Células , Humanos , Macrófagos , MicroRNAs/genética , Neoplasias Bucais/genética , Proteínas Serina-Treonina Quinases/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço , Proteínas Supressoras de Tumor
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(6): 536-540, 2021 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-34096020

RESUMO

OBJECTIVE: To construct the differential expression profile of microRNA (miRNA) in plasma of patients with type 2 diabetes mellitus (T2DM) and explore the possibility of using miRNA as the target for diagnosis and treatment of T2DM. METHODS: Agilent miRNA microarray was used to determine the expression profiles of miRNA in the plasma of patients with T2DM (FC> 2, P< 0.05). The result was verified by real-time quantitative PCR (RT-qPCR). Candidate miRNA was analyzed by bioinformatic tools. RESULTS: In total 122 differentially expressed miRNAs were identified. Among these, 14 were selected by multi-source intersection screening, which included 5 up-regulated genes and 9 down regulated genes. RT-qPCR showed that the expression of hsa-miR-185-5p and hsa-miR-328-5p have significantly increased in T2DM patients (P< 0.05). Bioinformatic analysis suggested that these miRNAs may be involved in the pathogenesis of T2DM through insulin secretion and PI3K-AKT signaling pathway. CONCLUSION: Differential expression of hsa-miR-185-5p and hsa-miR-328-5p in the plasma may be closely associated with the pathogenesis of T2DM.


Assuntos
Diabetes Mellitus Tipo 2 , MicroRNAs , Biologia Computacional , Diabetes Mellitus Tipo 2/genética , Humanos , MicroRNAs/genética , Fosfatidilinositol 3-Quinases , Transdução de Sinais
12.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068078

RESUMO

Anthracyclines remain a cornerstone of induction chemotherapy for acute myeloid leukemia (AML). Refractory or relapsed disease due to chemotherapy resistance is a major obstacle in AML management. MicroRNAs (miRNAs) have been observed to be involved in chemoresistance. We previously observed that miR-15a-5p was overexpressed in a subgroup of chemoresistant cytogenetically normal AML patients compared with chemosensitive patients treated with daunorubicin and cytarabine. MiR-15a-5p overexpression in AML cells reduced apoptosis induced by both drugs in vitro. This study aimed to elucidate the mechanisms by which miR-15a-5p contributes to daunorubicin resistance. We showed that daunorubicin induced autophagy in myeloid cell lines. The inhibition of autophagy reduced cell sensitivity to daunorubicin. The overexpression of miR-15a-5p decreased daunorubicin-induced autophagy. Conversely, the downregulation of miR-15a-5p increased daunorubicin-induced autophagy. We found that miR-15a-5p targeted four genes involved in autophagy, namely ATG9a, ATG14, GABARAPL1 and SMPD1. Daunorubicin increased the expression of these four genes, and miR-15a-5p counteracted this regulation. Inhibition experiments with the four target genes showed the functional effect of miR-15a-5p on autophagy. In summary, our results indicated that miR-15a-5p induces chemoresistance in AML cells through the abrogation of daunorubicin-induced autophagy, suggesting that miR-15a-5p could be a promising therapeutic target for chemoresistant AML patients.


Assuntos
Biomarcadores Tumorais/metabolismo , Daunorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Leucemia Mieloide Aguda/tratamento farmacológico , MicroRNAs/genética , Adulto , Antibióticos Antineoplásicos/farmacologia , Apoptose , Autofagia , Biomarcadores Tumorais/genética , Proliferação de Células , Perfilação da Expressão Gênica , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Células Tumorais Cultivadas
13.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068160

RESUMO

Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder occurring in susceptible individuals following a traumatic event. Understanding the mechanisms subserving trauma susceptibility/resilience is essential to develop new effective treatments. Increasing evidence suggests that non-coding RNAs, such as microRNAs (miRNAs), may play a prominent role in mediating trauma susceptibility/resilience. In this study, we evaluated the transcriptional expression of two key PTSD-related genes (FKBP5 and BDNF) and the relative targeting miRNAs (miR-15a-5p, miR-497a-5p, miR-511-5p, let-7d-5p) in brain areas of PTSD-related susceptible and resilient mice identified through our recently developed mouse model of PTSD (arousal-based individual screening (AIS) model). We observed lower transcript levels of miR-15a-5p, miR-497a-5p, and miR-511a-5p in the hippocampus and hypothalamus of susceptible mice compared to resilient mice, suggesting that the expression of these miRNAs could discriminate the two different phenotypes of stress-exposed mice. These miRNA variations could contribute, individually or synergically, to the inversely correlated transcript levels of FKBP5 and BDNF. Conversely, in the medial prefrontal cortex, downregulation of miR-15a-5p, miR-511-5p, and let-7d-5p was observed both in susceptible and resilient mice, and not accompanied by changes in their mRNA targets. Furthermore, miRNA expression in the different brain areas correlated to stress-induced behavioral scores (arousal score, avoidance-like score, social memory score and PTSD-like score), suggesting a linear connection between miRNA-based epigenetic modulation and stress-induced phenotypes. Pathway analysis of a miRNA network showed a statistically significant enrichment of molecular processes related to PTSD and stress. In conclusion, our results indicate that PTSD susceptibility/resilience might be shaped by brain-area-dependent modulation of miRNAs targeting FKBP5, BDNF, and other stress-related genes.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , MicroRNAs/genética , Resiliência Psicológica , Transtornos de Estresse Pós-Traumáticos/patologia , Proteínas de Ligação a Tacrolimo/metabolismo , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Regulação da Expressão Gênica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transtornos de Estresse Pós-Traumáticos/genética , Transtornos de Estresse Pós-Traumáticos/metabolismo , Proteínas de Ligação a Tacrolimo/genética
14.
Int J Mol Sci ; 22(10)2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-34068434

RESUMO

(1) Background: Understanding the function of circular RNAs (circRNAs), a class of noncoding RNA, in psoriatic skin can provide important insights into the complex regulation of genes contributing to the pathogenesis of psoriasis. (2) Methods: A novel method was applied to RNA-seq datasets from 93 skin biopsy samples to comprehensively identify circRNAs of all types, i.e., canonical circRNAs from the intron-exon junctions of mRNAs and interior circRNAs (i-circRNAs) from the interior regions of exons, introns, and intergenic regions. Selected circRNAs were experimentally validated by qRT-PCR and Sanger sequencing. CircRNAs with abundant and differential expression were identified and their putative function as competing endogenous RNAs (ceRNAs) was analyzed by an integrated analysis of circRNAs, microRNAs, and mRNAs. (3) Results: With a comprehensive search using no information of splicing signals, we systematically identified 179 highly abundant circRNAs in psoriatic skin. Many of these were reported for the first time and many were differentially expressed in involved versus normal or uninvolved skin. Validation based on three additional RNA-seq datasets confirmed most of the identified circRNAs in psoriatic skin. Experimental analyses confirmed the expression of the well-known circRNA CDR1as, a canonical circRNA, and a novel i-circRNA in psoriasis. We also identified many circRNAs that may act as ceRNAs to regulate the expression of mRNA genes in psoriasis-related signaling pathways in psoriasis. (4) Conclusions: The result of the study suggested that circRNAs are abundant in psoriatic skin, have distinct characteristics, and contribute to psoriatic pathogenesis.


Assuntos
Regulação da Expressão Gênica , MicroRNAs/metabolismo , Psoríase/genética , RNA Circular/genética , RNA Mensageiro/metabolismo , Pele/metabolismo , Estudos de Casos e Controles , Humanos , MicroRNAs/genética , Psoríase/patologia , RNA Circular/metabolismo , RNA Mensageiro/genética , RNA-Seq
15.
Sci Total Environ ; 784: 147182, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34088068

RESUMO

Cadmium (Cd) is associated with non-alcoholic fatty liver disease (NAFLD). The hepatic activation of p53/miR-43a-induced suppression of SIRT1/FXR axis plays a significant role in the development of NAFLD. In this study, we have investigated CdCl2-induced NAFLD in rats involves activation of miR34a/SIRT1/FXR axis. Adult male rats were divided into 4 groups (n-8/each) as a control, CdCl2 (10 mg/l), CdCl2 + miR-34a antagomir (inhibitor), and CdCl2 + SRT1720 (a SIRT1 activator) for 8 weeks, daily. With no effect on fasting glucose and insulin levels, CdCl2 significantly reduced rats' final body, fat pads, and liver weights, and food intake. Concomitantly, it increased the circulatory levels of liver markers (ALT, AST, and γ-GTT), increased the serum and hepatic levels of total cholesterol and triglycerides coincided with increased hepatic lipid accumulation. Besides, it increased the mRNA and protein levels of SREBP1, SREBP2, FAS, and HMGCOA reductase but reduced mRNA levels of PPARα, CPT1, and CPT2. Interestingly, CdCl2 also increased mRNA levels of miR34 without altering mRNA levels of SIRT1 but with a significant reduction in protein levels of SIRT1. These effects were associated with increased total protein levels of p53 and acetylated protein of p53, and FXR. Of note, suppressing miR-34a with a specific anatomic or activating SIRT1 by SRT1720 completely prevented all these effects and reduced hepatic fat accumulations in the livers of rats. In conclusion, CdCl2 induced NAFLD by increasing the transcription of miR-34a which in turn downregulates SIRT1 at the translational level.


Assuntos
Cloreto de Cádmio/efeitos adversos , MicroRNAs , Hepatopatia Gordurosa não Alcoólica , Animais , Fígado/metabolismo , Masculino , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/induzido quimicamente , Proteínas de Ligação a RNA , Ratos , Sirtuína 1/genética , Sirtuína 1/metabolismo , Proteína Supressora de Tumor p53
16.
J Int Med Res ; 49(6): 3000605211013207, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34102907

RESUMO

OBJECTIVE: To study the relationship between the circular RNA vesicle-associated membrane protein-associated protein A (circVAPA) and the pathogenesis of oral squamous cell carcinoma. METHODS: The expression of circVAPA was detected by RT-qPCR. In vitro loss-of-function experiments were performed in Cal-27 cells. The malignant phenotype of cells was evaluated by cell counting kit-8, clone formation and transwell assays. Luciferase reporter assays were used to assess the circVAPA/miR-132/homeobox A (HOXA) regulatory axis. RESULTS: circVAPA expression was significantly increased in oral cancer tissues and cells. The overall survival and progression-free survival of patients with oral cancer who exhibited high circVAPA expression were significantly shorter compared with those with low expression. circVAPA expression was closely related to tumor size, TNM stage and distant metastasis. circVAPA knockdown reduced the proliferation, invasion and migration of Cal-27 cells. MiR-132 was identified as a target of circVAPA in Cal-27 cells. Cotransfection with si-circVAPA and miR-132 inhibitor reversed the inhibitory effect of circVAPA knockdown on cell malignant phenotypes. HOXA7 was further identified as a downstream target of miR-132. CONCLUSION: circVAPA is highly expressed in oral cancer, and its abnormal expression might affect the proliferation, invasion and migration of oral cancer cells by modulating the miR-132/HOXA7 signaling axis.


Assuntos
Carcinoma de Células Escamosas , MicroRNAs , Neoplasias Bucais , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio , Humanos , MicroRNAs/genética , Neoplasias Bucais/genética
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(3): 757-762, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34105469

RESUMO

OBJECTIVE: To investigate the relationship between the polymorphism of miR-155 and its target gene MyD88 and clinicopathological features of diffuse large B-cell lymphoma (DLBCL). METHODS: 135 cases of DLBCL patients in our hospital from March 2015 to August 2017 were selected, and 90 cases of reactive hyperplasia of lymph nodes were selected as the control group. The relative expression of miR-155 and MyD88 gene polymorphism were detected in the two groups, and the relationship between miR-155 and MyD88 gene polymorphism and clinicopathological characteristics of DLBCL was analyzed. RESULTS: The relative expression of miR-155 in DLBCL patients was significantly higher than that in the control group (P<0.05). The mutation rate of MyD88 L265P in DLBCL group was significantly higher than that in control group (P<0.05). The relative expression of miR-155 in patients with MyD88 L265P mutation was significantly higher than that in patients with wild-type DLBCL (P<0.05). The relative expression of miR-155 and the polymorphism of MyD88 L265P were associated with lesion location, stage, BCL-2 protein expression and MyD88 protein expression in DLBCL patients (t=7.461、8.804、6.487、10.812; χ2=10.681、8.599、7.251、23.008;P<0.05). The survival of DLBCL patients with low miR-155 expression was significantly better than that with high miR-155 expression (P<0.05). The survival of wild-type DLBCL patients with MyD88 L265P locus was significantly better than that of mutant DLBCL patients (P<0.05). There was a significant positive correlation between the relative expression of miR-155 and the expression of MyD88 protein (r=0.428, P=0.000). CONCLUSION: The abnormal expression of miR-155 and the mutation rate of MyD88 gene in DLBCL patients are increased, and the expression of miR-155 and the mutation of MyD88 gene affect the disease progression and prognosis of patients, which may be potential biological indicators for the diagnosis, treatment and prognosis of DLBCL.


Assuntos
Linfoma Difuso de Grandes Células B , MicroRNAs , Humanos , Linfoma Difuso de Grandes Células B/genética , MicroRNAs/genética , Mutação , Fator 88 de Diferenciação Mieloide/genética , Polimorfismo Genético , Prognóstico
18.
BMC Bioinformatics ; 22(Suppl 10): 270, 2021 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-34058987

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of renal carcinoma and patients at advanced stage showed poor survival rate. Despite microRNAs (miRNAs) are used as potential biomarkers in many cancers, miRNA biomarkers for predicting the tumor stage of ccRCC are still limitedly identified. Therefore, we proposed a new integrated machine learning (ML) strategy to identify a novel miRNA signature related to tumor stage and prognosis of ccRCC patients using miRNA expression profiles. A multivariate Cox regression model with three hybrid penalties including Least absolute shrinkage and selection operator (Lasso), Adaptive lasso and Elastic net algorithms was used to screen relevant prognostic related miRNAs. The best subset regression (BSR) model was used to identify optimal prognostic model. Five ML algorithms were used to develop stage classification models. The biological significance of the miRNA signature was analyzed by utilizing DIANA-mirPath. RESULTS: A four-miRNA signature associated with survival was identified and the expression of this signature was strongly correlated with high risk patients. The high risk patients had unfavorable overall survival compared with the low risk group (HR = 4.523, P-value = 2.86e-08). Univariate and multivariate analyses confirmed independent and translational value of this predictive model. A combined ML algorithm identified six miRNA signatures for cancer staging prediction. After using the data balancing algorithm SMOTE, the Support Vector Machine (SVM) algorithm achieved the best classification performance (accuracy = 0.923, sensitivity = 0.927, specificity = 0.919, MCC = 0.843) when compared with other classifiers. Furthermore, enrichment analysis indicated that the identified miRNA signature involved in cancer-associated pathways. CONCLUSIONS: A novel miRNA classification model using the identified prognostic and tumor stage associated miRNA signature will be useful for risk and stage stratification for clinical practice, and the identified miRNA signature can provide promising insight to understand the progression mechanism of ccRCC.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , MicroRNAs , Carcinoma de Células Renais/genética , Humanos , Neoplasias Renais/genética , MicroRNAs/genética , Estadiamento de Neoplasias , Taxa de Sobrevida
19.
J Clin Invest ; 131(11)2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34060486

RESUMO

With increasing age, individuals are more vulnerable to viral infections such as with influenza or the SARS-CoV-2 virus. One age-associated defect in human T cells is the reduced expression of miR-181a. miR-181ab1 deficiency in peripheral murine T cells causes delayed viral clearance after infection, resembling human immune aging. Here we show that naive T cells from older individuals as well as miR-181ab1-deficient murine T cells develop excessive replication stress after activation, due to reduced histone expression and delayed S-phase cell cycle progression. Reduced histone expression was caused by the miR-181a target SIRT1 that directly repressed transcription of histone genes by binding to their promoters and reducing histone acetylation. Inhibition of SIRT1 activity or SIRT1 silencing increased histone expression, restored cell cycle progression, diminished the replication-stress response, and reduced the production of inflammatory mediators in replicating T cells from old individuals. Correspondingly, treatment with SIRT1 inhibitors improved viral clearance in mice with miR-181a-deficient T cells after LCMV infection. In conclusion, SIRT1 inhibition may be beneficial to treat systemic viral infection in older individuals by targeting antigen-specific T cells that develop replication stress due to miR-181a deficiency.


Assuntos
COVID-19/imunologia , Senescência Celular/imunologia , Histonas/deficiência , MicroRNAs/imunologia , SARS-CoV-2/imunologia , Linfócitos T/imunologia , Animais , COVID-19/genética , Senescência Celular/genética , Feminino , Histonas/imunologia , Humanos , Masculino , Camundongos Knockout , MicroRNAs/genética , SARS-CoV-2/genética , Sirtuína 1/genética , Sirtuína 1/imunologia
20.
BMC Res Notes ; 14(1): 234, 2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34134782

RESUMO

OBJECTIVE: Breast cancer (BC) is the most significant and lethal type of cancer in women. Although there are many newly develop chemotherapy drugs for patients with BC treating at various stages, drug resistance is the most important obstacle in their effectiveness for BC treatment. On the other hand, microRNAs are considered key regulators of genes involved in carcinogenesis and chemoresistance in cancers. The purpose of this study was to evaluate the role of miR-152-3p and miR-185 in intrinsic chemoresistance and proliferation of BC. In addition, the potential role of these miRNAs during chemoresistance was evaluated through possible signaling pathways. RESULTS: Here, miR-152-3p was significantly downregulated in tumor tissues compared to the corresponding margin tissues in patients with BC (p-value ≥ 0.04407 and fold change = - 2.0552). In contrast, no statistically significant difference was observed in the miR-185 expression between the two groups. Furthermore, no significant correlation was found between the expression of these two miRNAs and subfactors, including cancer family history, abortion, and age. Downregulation of miR-152-3p could be considered a promising regulator of BC chemoresistance.


Assuntos
Neoplasias da Mama , MicroRNAs , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Proliferação de Células , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Transdução de Sinais
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