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1.
Viruses ; 13(3)2021 03 03.
Artículo en Inglés | MEDLINE | ID: mdl-33802569

RESUMEN

The recently emerged SARS-CoV-2 virus is responsible for the ongoing COVID-19 pandemic that has rapidly developed into a global public health threat. Patients severely affected with COVID-19 present distinct clinical features, including acute respiratory disorder, neutrophilia, cytokine storm, and sepsis. In addition, multiple pro-inflammatory cytokines are found in the plasma of such patients. Transcriptome sequencing of different specimens obtained from patients suffering from severe episodes of COVID-19 shows dynamics in terms of their immune responses. However, those host factors required for SARS-CoV-2 propagation and the underlying molecular mechanisms responsible for dysfunctional immune responses during COVID-19 infection remain elusive. In the present study, we analyzed the mRNA-long non-coding RNA (lncRNA) co-expression network derived from publicly available SARS-CoV-2-infected transcriptome data of human lung epithelial cell lines and bronchoalveolar lavage fluid (BALF) from COVID-19 patients. Through co-expression network analysis, we identified four differentially expressed lncRNAs strongly correlated with genes involved in various immune-related pathways crucial for cytokine signaling. Our findings suggest that the aberrant expression of these four lncRNAs can be associated with cytokine storms and anti-viral responses during severe SARS-CoV-2 infection of the lungs. Thus, the present study uncovers molecular interactions behind the cytokine storm activation potentially responsible for hyper-inflammatory responses in critical COVID-19 patients.


Asunto(s)
/genética , ARN Largo no Codificante/genética , ARN Mensajero/genética , /fisiología , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/genética , Citocinas/inmunología , Redes Reguladoras de Genes , Humanos , Pulmón/inmunología , Pulmón/virología , ARN Largo no Codificante/inmunología , ARN Mensajero/inmunología , /genética
2.
Int J Mol Sci ; 22(6)2021 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-33809601

RESUMEN

Recurrent implantation failure (RIF) refers to the occurrence of more than two failed in vitro fertilization-embryo transfers (IVF-ETs) in the same individual. RIF can occur for many reasons, including embryo characteristics, immunological factors, and coagulation factors. Genetics can also contribute to RIF, with some single-nucleotide variants (SNVs) reported to be associated with RIF occurrence. We examined SNVs in a long non-coding RNA, homeobox (HOX) transcript antisense RNA (HOTAIR), which is known to affect cancer development. HOTAIR regulates epigenetic outcomes through histone modifications and chromatin remodeling. We recruited 155 female RIF patients and 330 healthy controls, and genotyped HOTAIR SNVs, including rs4759314, rs920778, rs7958904, and rs1899663, in all participants. Differences in these SNVs were compared between the patient and control groups. We identified significant differences in the occurrence of heterozygous genotypes and the dominant expression model for the rs1899663 and rs7958904 SNVs between RIF patients and control subjects. These HOTAIR variants were associated with serum hemoglobin (Hgb), luteinizing hormone (LH), total cholesterol (T. chol), and blood urea nitrogen (BUN) levels, as assessed by analysis of variance (ANOVA). We analyzed the four HOTAIR SNVs and found significant differences in haplotype patterns between RIF patients and healthy controls. The results of this study showed that HOTAIR is not only associated with the development of cancer but also with pregnancy-associated diseases. This study represents the first report showing that HOTAIR is correlated with RIF.


Asunto(s)
Fertilización In Vitro , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , ARN Largo no Codificante/genética , Adulto , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes/genética , Humanos , Desequilibrio de Ligamiento/genética , Recurrencia , Insuficiencia del Tratamiento
3.
Int J Mol Sci ; 22(6)2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33809362

RESUMEN

Enteroviruses (EVs) are common RNA viruses that can cause various types of human diseases and conditions such as hand, foot, and mouth disease (HFMD), myocarditis, meningitis, sepsis, and respiratory disorders. Although EV infections in most patients are generally mild and self-limiting, a small number of young children can develop serious complications such as encephalitis, acute flaccid paralysis, myocarditis, and cardiorespiratory failure, resulting in fatalities. Established evidence has suggested that certain non-coding RNAs (ncRNAs) such as microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) are involved in the occurrence and progression of many human diseases. Recently, the involvement of ncRNAs in the course of EV infection has been reported. Herein, the authors focus on recent advances in the understanding of ncRNAs in EV infection from basic viral pathogenesis to clinical prospects, providing a reference basis and new ideas for disease prevention and research directions.


Asunto(s)
Infecciones por Enterovirus/genética , Enterovirus/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Antígenos Virales/genética , Niño , Enterovirus/patogenicidad , Infecciones por Enterovirus/virología , Humanos , ARN Circular/genética , ARN no Traducido/genética
4.
BMC Genomics ; 22(1): 275, 2021 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-33863291

RESUMEN

BACKGROUND: Sepsis is the major cause of death in Intensive Care Unit (ICU) globally. Molecular detection enables rapid diagnosis that allows early intervention to minimize the death rate. Recent studies showed that long non-coding RNAs (lncRNAs) regulate proinflammatory genes and are related to the dysfunction of organs in sepsis. Identifying lncRNA signature with absolute abundance is challenging because of the technical variation and the systematic experimental bias. RESULTS: Cohorts (n = 768) containing whole blood lncRNA profiling of sepsis patients in the Gene Expression Omnibus (GEO) database were included. We proposed a novel diagnostic strategy that made use of the relative expressions of lncRNA pairs, which are reversed between sepsis patients and normal controls (eg. lncRNAi > lncRNAj in sepsis patients and lncRNAi < lncRNAj in normal controls), to identify 14 lncRNA pairs as a sepsis diagnostic signature. The signature was then applied to independent cohorts (n = 644) to evaluate its predictive performance across different ages and normalization methods. Comparing to common machine learning models and existing signatures, SepSigLnc consistently attains better performance on the validation cohorts from the same age group (AUC = 0.990 & 0.995 in two cohorts) and across different groups (AUC = 0.878 on average), as well as cohorts processed by an alternative normalization method (AUC = 0.953 on average). Functional analysis demonstrates that the lncRNA pairs in SepsigLnc are functionally similar and tend to implicate in the same biological processes including cell fate commitment and cellular response to steroid hormone stimulus. CONCLUSION: Our study identified 14 lncRNA pairs as signature that can facilitate the diagnosis of septic patients at an intervenable point when clinical manifestations are not dramatic. Also, the computational procedure can be generalized to a standard procedure for discovering diagnostic molecule signatures.


Asunto(s)
Neoplasias Encefálicas/mortalidad , ARN Largo no Codificante/genética , Sepsis/diagnóstico , Estudios de Cohortes , Humanos , Sepsis/genética
5.
BMC Bioinformatics ; 22(1): 175, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33794766

RESUMEN

BACKGROUND: Identifying lncRNA-disease associations not only helps to better comprehend the underlying mechanisms of various human diseases at the lncRNA level but also speeds up the identification of potential biomarkers for disease diagnoses, treatments, prognoses, and drug response predictions. However, as the amount of archived biological data continues to grow, it has become increasingly difficult to detect potential human lncRNA-disease associations from these enormous biological datasets using traditional biological experimental methods. Consequently, developing new and effective computational methods to predict potential human lncRNA diseases is essential. RESULTS: Using a combination of incremental principal component analysis (IPCA) and random forest (RF) algorithms and by integrating multiple similarity matrices, we propose a new algorithm (IPCARF) based on integrated machine learning technology for predicting lncRNA-disease associations. First, we used two different models to compute a semantic similarity matrix of diseases from a directed acyclic graph of diseases. Second, a characteristic vector for each lncRNA-disease pair is obtained by integrating disease similarity, lncRNA similarity, and Gaussian nuclear similarity. Then, the best feature subspace is obtained by applying IPCA to decrease the dimension of the original feature set. Finally, we train an RF model to predict potential lncRNA-disease associations. The experimental results show that the IPCARF algorithm effectively improves the AUC metric when predicting potential lncRNA-disease associations. Before the parameter optimization procedure, the AUC value predicted by the IPCARF algorithm under 10-fold cross-validation reached 0.8529; after selecting the optimal parameters using the grid search algorithm, the predicted AUC of the IPCARF algorithm reached 0.8611. CONCLUSIONS: We compared IPCARF with the existing LRLSLDA, LRLSLDA-LNCSIM, TPGLDA, NPCMF, and ncPred prediction methods, which have shown excellent performance in predicting lncRNA-disease associations. The compared results of 10-fold cross-validation procedures show that the predictions of the IPCARF method are better than those of the other compared methods.


Asunto(s)
Biología Computacional , Aprendizaje Automático , ARN Largo no Codificante , Algoritmos , Humanos , Análisis de Componente Principal , ARN Largo no Codificante/genética
6.
BMC Bioinformatics ; 22(1): 217, 2021 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-33910497

RESUMEN

BACKGROUND: lncRNA may be involved in the occurrence, metastasis, and chemical reaction of hepatocellular carcinoma (HCC) through various pathways associated with autophagy. Therefore, it is urgent to reveal more autophagy-related lncRNAs, explore these lncRNAs' clinical significance, and find new targeted treatment strategies. METHODS: The corresponding data of HCC patients and autophagy genes were obtained from the TCGA database, and the human autophagy database respectively. Based on the co-expression and Cox regression analysis to construct prognostic prediction signature. RESULTS: Finally, a signature containing seven autophagy-related lncRNAs (PRRT3-AS1, RP11-479G22.8, RP11-73M18.8, LINC01138, CTD-2510F5.4, CTC-297N7.9, RP11-324I22.4) was constructed. Based on the risk score of signature, Overall survival (OS) curves show that the OS of high-risk patients is significantly lower than that of low-risk patients (P = 2.292e-10), and the prognostic prediction accuracy of risk score (AUC = 0.786) is significantly higher than that of ALBI (0.532), child_pugh (0.573), AFP (0.5751), and AJCC_stage (0.631). Moreover, multivariate Cox analysis and Nomogram of risk score are indicated that the 1-year and 3-year survival rates of patients are obviously accuracy by the combined analysis of the risk score, child_pugh, age, M_stage, and Grade (The AUC of 1- and 3-years are 0.87, and 0.855). Remarkably, the 7 autophagy-related lncRNAs may participate in Spliceosome, Cell cycle, RNA transport, DNA replication, and mRNA surveillance pathway and be related to the biological process of RNA splicing and mRNA splicing. CONCLUSION: In conclusion, the 7 autophagy-related lncRNAs might be promising prognostic and therapeutic targets for HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , ARN Largo no Codificante , Autofagia , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Niño , Preescolar , Humanos , Lactante , Neoplasias Hepáticas/genética , Pronóstico , ARN Largo no Codificante/genética
7.
Int J Mol Sci ; 22(6)2021 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-33805611

RESUMEN

Plants have evolved diverse molecular mechanisms that enable them to respond to a wide range of pathogens. It has become clear that microRNAs, a class of short single-stranded RNA molecules that regulate gene expression at the transcriptional or post-translational level, play a crucial role in coordinating plant-pathogen interactions. Specifically, miRNAs have been shown to be involved in the regulation of phytohormone signals, reactive oxygen species, and NBS-LRR gene expression, thereby modulating the arms race between hosts and pathogens. Adding another level of complexity, it has recently been shown that specific lncRNAs (ceRNAs) can act as decoys that interact with and modulate the activity of miRNAs. Here we review recent findings regarding the roles of miRNA in plant defense, with a focus on the regulatory modes of miRNAs and their possible applications in breeding pathogen-resistance plants including crops and trees. Special emphasis is placed on discussing the role of miRNA in the arms race between hosts and pathogens, and the interaction between disease-related miRNAs and lncRNAs.


Asunto(s)
Regulación de la Expresión Génica de las Plantas/inmunología , Interacciones Huésped-Patógeno/genética , MicroARNs/genética , Enfermedades de las Plantas/genética , Inmunidad de la Planta/genética , Proteínas de Plantas/genética , Plantas/genética , Interacciones Huésped-Patógeno/inmunología , MicroARNs/inmunología , Hongos Mitospóricos/genética , Hongos Mitospóricos/crecimiento & desarrollo , Hongos Mitospóricos/patogenicidad , Fitomejoramiento/métodos , Enfermedades de las Plantas/inmunología , Enfermedades de las Plantas/microbiología , Reguladores del Crecimiento de las Plantas/inmunología , Reguladores del Crecimiento de las Plantas/metabolismo , Proteínas de Plantas/inmunología , Plantas/inmunología , Plantas/microbiología , ARN Largo no Codificante/genética , ARN Largo no Codificante/inmunología , ARN de Planta/genética , ARN de Planta/inmunología , Especies Reactivas de Oxígeno/inmunología , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal
8.
Nat Genet ; 53(4): 551-563, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33821005

RESUMEN

Polycomb repressive complexes 1 and 2 (PRC1/2) maintain transcriptional silencing of developmental genes largely by catalyzing the formation of mono-ubiquitinated histone H2A at lysine 119 (H2AK119ub1) and trimethylated histone H3 at lysine 27 (H3K27me3), respectively. How Polycomb domains are reprogrammed during mammalian preimplantation development remains largely unclear. Here we show that, although H2AK119ub1 and H3K27me3 are highly colocalized in gametes, they undergo differential reprogramming dynamics following fertilization. H3K27me3 maintains thousands of maternally biased domains until the blastocyst stage, whereas maternally biased H2AK119ub1 distribution in zygotes is largely equalized at the two-cell stage. Notably, while maternal PRC2 depletion has a limited effect on global H2AK119ub1 in early embryos, it disrupts allelic H2AK119ub1 at H3K27me3 imprinting loci including Xist. By contrast, acute H2AK119ub1 depletion in zygotes does not affect H3K27me3 imprinting maintenance, at least by the four-cell stage. Importantly, loss of H2AK119ub1, but not H3K27me3, causes premature activation of developmental genes during zygotic genome activation (ZGA) and subsequent embryonic arrest. Thus, our study reveals distinct dynamics and functions of H3K27me3 and H2AK119ub1 in mouse preimplantation embryos.


Asunto(s)
Blastocisto/metabolismo , Epigénesis Genética , Regulación del Desarrollo de la Expresión Génica , Histonas/genética , Herencia Materna , ARN Largo no Codificante/genética , Animales , Blastocisto/citología , Femenino , Fertilización/genética , Histonas/metabolismo , Lisina/metabolismo , Masculino , Ratones , Oocitos/citología , Oocitos/crecimiento & desarrollo , Oocitos/metabolismo , Herencia Paterna , Complejo Represivo Polycomb 1/genética , Complejo Represivo Polycomb 1/metabolismo , Complejo Represivo Polycomb 2/genética , Complejo Represivo Polycomb 2/metabolismo , Embarazo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , ARN Largo no Codificante/metabolismo , Espermatozoides/citología , Espermatozoides/metabolismo , Ubiquitinación , Cigoto/citología , Cigoto/crecimiento & desarrollo , Cigoto/metabolismo
9.
World J Surg Oncol ; 19(1): 121, 2021 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-33865414

RESUMEN

BACKGROUND: It has been reported that long-chain non-coding RNA (lncRNA) zinc finger E-box binding homeobox 1 antisense 1 (ZEB1-AS1) is an oncogene in various cancers, including hepatocellular carcinoma (HCC). We investigated the role and mechanism of ZEB1-AS1 as a competitive endogenous RNA (ceRNA) combined with miR-23c in HCC cell proliferation and invasion. METHODS: QRT-PCR was used to detect ZEB1-AS1 and miR-23c expressions in HCC tissues and cells. The dual luciferase reporter assay detected the targeted regulation of miR-23c and ZEB1-AS1. We also performed the correlation analysis of their expression in HCC tissues by the Spearman's correlation analysis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the proliferation of hepatoma cells. Cell invasion was assessed by the Transwell assay. RESULTS: QRT-PCR results indicated ZEB1-AS1 was upregulated and miR-23c was downregulated in HCC tissues and cell lines. ZEB1-AS1 knockdown hampered the proliferation and invasion of HCC cells. Dual luciferase reporter assay showed that miR-23c is a target of ZEB1-AS1, and ZEB1-AS1 was significantly negatively correlated with the miR-23c expression in HCC tissues. The results of MTT and Transwell assay showed that miR-23c inhibition restored the inhibitory effect of ZEB1-AS1 knockdown on HCC cells proliferation and invasion. CONCLUSIONS: As a ceRNA, lncRNA ZEB1-AS1 may play a vital role in inhibiting HCC progression through miR-23c, which will provide new clues and theoretical basis for the HCC diagnosis and treatment.


Asunto(s)
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , ARN Largo no Codificante/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Apoptosis/genética , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Proliferación Celular/genética , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Hepáticas/patología , MicroARNs/genética , Pronóstico
10.
World J Surg Oncol ; 19(1): 122, 2021 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-33865422

RESUMEN

BACKGROUND AND OBJECTIVES: Long non-coding RNA (lncRNA) prostate androgen-regulated transcript 1 (PART1) was previously shown to exert an oncogenic role in several human cancers. However, whether PART1 is associated with the malignant progression of pancreatic cancer remains unclear. In the current study, we aimed to identify the role and potential mechanism of PART1 in pancreatic cancer. METHODS: qRT-PCR was applied to detect PART1 expression in 45 cases of pancreatic cancer patients. The chi-square test was performed to assess the association between PART1 expression and clinicopathologic features, and Kaplan-Meier method was applied to evaluate overall survival. In vitro CCK-8, transwell invasion, and flow cytometry assays were applied to detect the effects of PART1 on cell proliferation, invasion, and apoptosis, respectively. Luciferase reporter and RNA immunoprecipitation assays were used to identify the regulatory mechanism between PART1 and miR-122. RESULTS: PART1 expression was upregulated in pancreatic cancer tissues and cell lines. High PART1 expression was closely correlated with tumor size, T classification, clinical stage, and vascular invasion, and predicted a poor overall survival. PART1 knockdown significantly suppressed cell proliferation and invasion abilities of pancreatic cancer but promoted cell apoptosis. PART1 was found to serve as a molecular sponge of miR-122, and miR-122 inhibition partially reversed the inhibitory phenotypes of PART1 knockdown on pancreatic cancer cells. CONCLUSIONS: PART1 promotes the malignant progression of pancreatic cancer by sponging miR-122. The PART1/miR-122 axis might be a promising target for anticancer therapy in patients with pancreatic cancer.


Asunto(s)
Proliferación Celular/genética , MicroARNs/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN no Traducido/genética , Andrógenos , Línea Celular Tumoral , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , MicroARNs/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidad , Pronóstico
11.
Int J Mol Sci ; 22(5)2021 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-33800928

RESUMEN

Long non-coding RNAs (lncRNAs) play important roles in multiple biological processes including ovarian follicular development. Here we aimed to gain novel information regarding lncRNAs transcriptome profiles in porcine granulosa cells of advanced atretic antral (AA) and healthy antral (HA) follicles using RNA-seq. A total of 11,321 lncRNAs including 10,813 novel and 508 annotated lncRNAs were identified, of which 173 lncRNAs were differentially expressed (DE-lncRNAs); ten of these were confirmed by qRT-PCR. Gene Ontology indicated that DE-lncRNAs associated with developmental processes were highly enriched. Pathway analysis demonstrated predicted cis- and trans-targets of DE-lncRNAs. Potential mRNA targets of up-regulated DE-lncRNAs were mainly enriched in apoptosis related pathways, while targeted genes of downregulated DE-lncRNAs were primarily enriched in metabolism and ovarian steroidogenesis pathways. Linear regression analyses showed that expression of upregulated DE-lncRNAs was significantly associated with apoptosis related genes. NOVEL_00001850 is the most-downregulated DE-lncRNA (FDR = 0.04, FC = -6.53), of which miRNA binding sites were predicted. KEGG analysis of its downregulated target genes revealed that ovarian steroidogenesis was the second most highlighted pathway. qRT-PCR and linear regression analysis confirmed the expression and correlation of its potential targeted gene, CYP19A1, a key gene involved in estradiol synthesis. Our results indicate that lncRNAs may participate in granulosa cells apoptosis and thus antral follicular atresia.


Asunto(s)
Apoptosis/genética , Células de la Granulosa/metabolismo , Folículo Ovárico/metabolismo , ARN Largo no Codificante/genética , Animales , Ciclo Estral/genética , Femenino , Regulación de la Expresión Génica , Ontología de Genes , Modelos Lineales , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Porcinos , Transcriptoma , Regulación hacia Arriba
12.
Int J Mol Sci ; 22(6)2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33803955

RESUMEN

MicroRNAs (miRs) are non-coding master regulators of transcriptome that could act as tumor suppressors (TSs) or oncogenes (oncomiRs). We aimed to systematically investigate the relevance of miRs as prognostic biomarkers in primary glioblastoma multiforme (GBM) treated with postoperative radio(chemo)therapy (PORT). For hypothesis generation, tumor miR expression by Agilent 8x15K human microRNA microarrays and survival data from 482 GBM patients of The Cancer Genome Atlas (TCGA cohort) were analyzed using Cox-PH models. Expression of candidate miRs with prognostic relevance (miR-221/222; miR-17-5p, miR-18a, miR-19b) was validated by qRT-PCR using Taqman technology on an independent validation cohort of GBM patients (n = 109) treated at Heidelberg University Hospital (HD cohort). In TCGA, 50 miRs showed significant association with survival. Among the top ranked prognostic miRs were members of the two miR families miR-221/222 and miR-17-92. Loss of miR-221/222 was correlated with improved prognosis in both cohorts (TCGA, HD) and was an independent prognostic marker in a multivariate analysis considering demographic characteristics (age, sex, Karnofsky performance index (KPI)), molecular markers (O-6-methylguanine-DNA methyltransferase (MGMT) methylation, IDH mutation status) and PORT as co-variables. The prognostic value of miR-17-92 family members was ambiguous and in part contradictory by direct comparison of the two cohorts, thus warranting further validation in larger prospective trials.


Asunto(s)
Glioblastoma/radioterapia , MicroARNs/genética , ARN Largo no Codificante/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Supervivencia sin Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Glioblastoma/genética , Glioblastoma/patología , Glioblastoma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Regiones Promotoras Genéticas/genética , Análisis de Matrices Tisulares , Transcriptoma/genética
13.
Int J Mol Sci ; 22(6)2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33809929

RESUMEN

The occurrence of distant tumor metastases is a major barrier in non-small cell lung cancer (NSCLC) therapy, and seriously affects clinical treatment and patient prognosis. Recently, long non-coding RNAs (lncRNAs) have been demonstrated to be crucial regulators of metastasis in lung cancer. The aim of this study was to reveal the underlying mechanisms of a novel lncRNA LNC CRYBG3 in regulating NSCLC metastasis. Experimental results showed that LNC CRYBG3 was upregulated in NSCLC cells compared with normal tissue cells, and its level was involved in these cells' metastatic ability. Exogenously overexpressed LNC CRYBG3 increased the metastatic ability and the protein expression level of the metastasis-associated proteins Snail and Vimentin in low metastatic lung cancer HCC827 cell line. In addition, LNC CRYBG3 contributed to HCC827 cell metastasis in vivo. Mechanistically, LNC CRYBG3 could directly combine with eEF1A1 and promote it to move into the nucleus to enhance the transcription of MDM2. Overexpressed MDM2 combined with MDM2 binding protein (MTBP) to reduce the binding of MTBP with ACTN4 and consequently increased cell migration mediated by ACTN4. In conclusion, the LNC CRYBG3/eEF1A1/MDM2/MTBP axis is a novel signaling pathway regulating tumor metastasis and may be a potential therapeutic target for NSCLC treatment.


Asunto(s)
Proteínas Portadoras/metabolismo , Cristalinas/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Factor 1 de Elongación Peptídica/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , ARN Largo no Codificante/metabolismo , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/patología , Ratones Endogámicos NOD , Ratones SCID , Metástasis de la Neoplasia , Unión Proteica , ARN Largo no Codificante/genética , Transducción de Señal , Ensayos Antitumor por Modelo de Xenoinjerto
14.
Adv Exp Med Biol ; 1308: 13-23, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33861433

RESUMEN

Phytochemicals are various compounds produced by plants. There is growing evidence on their potential health effects. Some of these compounds are considered as traditional medicines and used as painkillers, anti-inflammatory agents, and for other applications. One of these phytochemicals is curumin, a natural polyphenol derived from the turmeric plant (Curcuma longa L.). Curcumin is widely used as a food coloring, preservative and condiment. It has also been shown to have antioxidative and anti-inflammatory effects. Moreover, there is growing evidence that curcumin alters long noncoding RNAs (lncRNAs) in many kinds of cancer. These noncoding RNAs can cause epigenetic modulation in the expression of several genes. This study reviews reports of curcumin effects on lncRNAs in lung, prostate, colorectal, breast, pancreatic, renal, gastric, and ovarian cancers.


Asunto(s)
Curcumina , Neoplasias , ARN Largo no Codificante , Antiinflamatorios/uso terapéutico , Curcumina/farmacología , Curcumina/uso terapéutico , Humanos , Masculino , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Fitoquímicos/uso terapéutico , ARN Largo no Codificante/genética , ARN Largo no Codificante/uso terapéutico
15.
Artículo en Inglés | MEDLINE | ID: mdl-33799753

RESUMEN

The aim of the current study is to investigate potential associations among Long Noncoding RNA (LncRNA) H19 single nucleotide polymorphism (SNP) and epidermal growth factor receptor (EGFR) phenotypes on the clinicopathological characteristics of lung adenocarcinoma (LADC). Five loci of LncRNA H19 SNPs (rs217727, rs2107425, rs2839698, rs3024270, and rs3741219) were genotyped by using TaqMan allelic discrimination in 223 LADC patients with wild-type EGFR phenotype and 323 LADC individuals with EGFR mutations. After the statistical analyses, patients with the EGFR mutation were related to a higher distribution frequency of rs217727 SNP CT heterozygote (p = 0.030), and the female population with EGFR mutation demonstrated a higher distribution frequency of rs217727 SNP CT heterozygote (p < 0.001) and rs2107425 CT heterozygote (p = 0.002). In addition, the presence of LncRNA H19 SNP rs217727 T allele (CT + TT) in patients with EGFR wild-type was associated to higher tumor T status (stage III or IV, p = 0.037) and poorer cell differentiation status (poor differentiation, p = 0.012) compared to those EGFR wild-type individuals with LncRNA H19 SNP rs217727 CC allele. Besides, a prominently higher tumor T status was found in subjects with LncRNA H19 SNP rs2107425 T allele (CT + TT) (stage III or IV, p = 0.007) compared to EGFR wild-type LADC individuals with LncRNA CC allele in EGFR wild-type patients. Our findings suggest that the presence of LncRNA H19 SNP rs217727 is related to the EGFR mutation in LADC patients, and the LncRNA H19 SNP rs217727 and rs2107425 are associated with progressed tumor status for LADC patients with EGFR wild-type.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , ARN Largo no Codificante , Adenocarcinoma del Pulmón/genética , Estudios de Casos y Controles , Receptores ErbB/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Neoplasias Pulmonares/genética , Fenotipo , Polimorfismo de Nucleótido Simple , ARN Largo no Codificante/genética
16.
Sheng Li Xue Bao ; 73(2): 253-262, 2021 Apr 25.
Artículo en Chino | MEDLINE | ID: mdl-33903887

RESUMEN

The aim of this study was to investigate the effects of dexmedetomidine (Dex) on hepatic ischemia/reperfusion injury (HIRI) and the underlying mechanism. The in vitro HIRI was induced by culturing HL-7702 cells, a human hepatocyte cell line, under 24 h of hypoxia and 12 h of reoxygenation. Quantitative real time PCR (qRT-PCR) and Western blot were performed to detect the expression levels of long non-coding RNA MALAT1, microRNA-126-5p (miR-126-5p) and high mobility group box-1 (HMGB1). Bioinformatics prediction and double luciferase assay were used to verify the targeting relationship between miR-126-5p and MALAT1, HMGB1. Reactive oxygen species (ROS), malondialdehyde (MDA) and ATP levels in culture medium were detected by corresponding kits. The results showed that Dex significantly reduced the levels of ROS and MDA, but increased the level of ATP in HL-7702 cells with HIRI. HIRI up-regulated the expression levels of MALAT1 and HMGB1, and down-regulated the level of miR-126-5p. Dex reversed these effects of HIRI. Furthermore, Dex inhibited HIRI-induced cellular apoptosis, whereas MALAT1 reversed the effect of Dex. This inhibitory effect of Dex could be restored by up-regulation of miR-126-5p. The results suggest that Dex protects hepatocytes from HIRI via regulating MALAT1/miR-126-5p/HMGB1 axis.


Asunto(s)
Dexmedetomidina , Proteína HMGB1 , MicroARNs , ARN Largo no Codificante , Daño por Reperfusión , Dexmedetomidina/farmacología , Proteína HMGB1/genética , Humanos , MicroARNs/genética , ARN Largo no Codificante/genética , Daño por Reperfusión/genética
17.
Mol Cell ; 81(8): 1598-1600, 2021 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-33861949

RESUMEN

Yu et al. (2021) demonstrate that a subset of X-linked immune genes is repressed on the inactive X chromosome (Xi) in a manner dependent on XIST RNA in B cells, and derepression of these genes upon XIST depletion could bias differentiation of naive B cells and be involved in etiology of female-biased autoimmune diseases.


Asunto(s)
ARN Largo no Codificante , Inactivación del Cromosoma X , Linfocitos B , Diferenciación Celular , Femenino , Humanos , ARN Largo no Codificante/genética , Cromosoma X/genética , Inactivación del Cromosoma X/genética
18.
Anticancer Res ; 41(4): 1761-1769, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33813380

RESUMEN

BACKGROUND: Clinical significance of plasma urothelial carcinoma associated 1 (UCA1) in patients with colorectal cancer (CRC) remains unclear. This study investigated the usefulness of plasma UCA1 as a biomarker in patients with CRC. MATERIALS AND METHODS: UCA1 levels were measured in the plasma and tissue from patients with CRC by quantitative polymerase chain reaction. Relationships between plasma UCA1 and clinicopathological features were examined. RESULTS: Plasma UCA1 levels were significantly lower in patients with CRC than in healthy volunteers. UCA1 expression in B-Raf proto-oncogene serine/threonine kinase (BRAF)-mutant CRC tissue was also lower than that in non-cancerous tissue, although it was higher in CRC with wild-type BRAF. In right-sided CRC, a lower plasma UCA1 level was associated with pT4 and BRAF mutation. In contrast, in left-sided CRC, higher plasma UCA1 was associated with pT4 and pStage 3b-4. CONCLUSION: Plasma UCA1 is a useful biomarker for CRC detection and predicting clinicopathological features, particularly BRAF mutation.


Asunto(s)
Biomarcadores de Tumor/genética , Ácidos Nucleicos Libres de Células/genética , Neoplasias Colorrectales/genética , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , ARN Largo no Codificante/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Estudios de Casos y Controles , Ácidos Nucleicos Libres de Células/sangre , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/patología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Fenotipo , ARN Largo no Codificante/sangre
19.
Nat Commun ; 12(1): 2038, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33795683

RESUMEN

Wild-type KRAS (KRASWT) amplification has been shown to be a secondary means of KRAS activation in cancer and associated with poor survival. Nevertheless, the precise role of KRASWT overexpression in lung cancer progression is largely unexplored. Here, we identify and characterize a KRAS-responsive lncRNA, KIMAT1 (ENSG00000228709) and show that it correlates with KRAS levels both in cell lines and in lung cancer specimens. Mechanistically, KIMAT1 is a MYC target and drives lung tumorigenesis by promoting the processing of oncogenic microRNAs (miRNAs) through DHX9 and NPM1 stabilization while halting the biogenesis of miRNAs with tumor suppressor function via MYC-dependent silencing of p21, a component of the Microprocessor Complex. KIMAT1 knockdown suppresses not only KRAS expression but also KRAS downstream signaling, thereby arresting lung cancer growth in vitro and in vivo. Taken together, this study uncovers a role for KIMAT1 in maintaining a positive feedback loop that sustains KRAS signaling during lung cancer progression and provides a proof of principle that interfering with KIMAT1 could be a strategy to hamper KRAS-induced tumorigenesis.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , MicroARNs/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , ARN Largo no Codificante/genética , Células A549 , Animales , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/terapia , Línea Celular Tumoral , Femenino , Perfilación de la Expresión Génica/métodos , Ontología de Genes , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Ratones Endogámicos NOD , Ratones Noqueados , Ratones SCID , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
20.
Mediators Inflamm ; 2021: 6635925, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33833618

RESUMEN

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was initially identified in China and currently worldwide dispersed, resulting in the coronavirus disease 2019 (COVID-19) pandemic. Notably, COVID-19 is characterized by systemic inflammation. However, the potential mechanisms of the "cytokine storm" of COVID-19 are still limited. In this study, fourteen peripheral blood samples from COVID-19 patients (n = 10) and healthy donors (n = 4) were collected to perform the whole-transcriptome sequencing. Lung tissues of COVID-19 patients (70%) presenting with ground-glass opacity. Also, the leukocytes and lymphocytes were significantly decreased in COVID-19 compared with the control group (p < 0.05). In total, 25,482 differentially expressed messenger RNAs (DE mRNA), 23 differentially expressed microRNAs (DE miRNA), and 410 differentially expressed long noncoding RNAs (DE lncRNAs) were identified in the COVID-19 samples compared to the healthy controls. Gene Ontology (GO) analysis showed that the upregulated DE mRNAs were mainly involved in antigen processing and presentation of endogenous antigen, positive regulation of T cell mediated cytotoxicity, and positive regulation of gamma-delta T cell activation. The downregulated DE mRNAs were mainly concentrated in the glycogen biosynthetic process. We also established the protein-protein interaction (PPI) networks of up/downregulated DE mRNAs and identified 4 modules. Functional enrichment analyses indicated that these module targets were associated with positive regulation of cytokine production, cytokine-mediated signaling pathway, leukocyte differentiation, and migration. A total of 6 hub genes were selected in the PPI module networks including AKT1, TNFRSF1B, FCGR2A, CXCL8, STAT3, and TLR2. Moreover, a competing endogenous RNA network showed the interactions between lncRNAs, mRNAs, and miRNAs. Our results highlight the potential pathogenesis of excessive cytokine production such as MSTRG.119845.30/hsa-miR-20a-5p/TNFRSF1B, MSTRG.119845.30/hsa-miR-29b-2-5p/FCGR2A, and MSTRG.106112.2/hsa-miR-6501-5p/STAT3 axis, which may also play an important role in the development of ground-glass opacity in COVID-19 patients. This study gives new insights into inflammation regulatory mechanisms of coding and noncoding RNAs in COVID-19, which may provide novel diagnostic biomarkers and therapeutic avenues for COVID-19 patients.


Asunto(s)
/sangre , ARN/sangre , ARN/genética , Adulto , Anciano , Estudios de Casos y Controles , Síndrome de Liberación de Citoquinas/sangre , Síndrome de Liberación de Citoquinas/etiología , Síndrome de Liberación de Citoquinas/genética , Citocinas/biosíntesis , Citocinas/genética , Femenino , Expresión Génica , Humanos , Mediadores de Inflamación/sangre , Masculino , MicroARNs/sangre , MicroARNs/genética , Persona de Mediana Edad , Pandemias , Mapas de Interacción de Proteínas/genética , ARN Largo no Codificante/sangre , ARN Largo no Codificante/genética , ARN Mensajero/sangre , ARN Mensajero/genética , Análisis de Secuencia de ARN , Transducción de Señal , Secuenciación del Exoma Completo , Adulto Joven
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