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Colorectal cancer (CRC) ranks the 3rd in cancer types globally. Long noncoding RNAs (lncRNAs) are related to the initiation and progression of CRC. The current study plans to reveal the action of rhabdomyosarcoma 2-associated transcript (RMST) in CRC. The results show that RMST is downregulated in CRC specimens and cell lines relative to normal specimens and a fetal normal colon cell line (FHC), respectively. Elevation of RMST represses cell proliferation and colony formation and induces cell apoptosis in CRC cells. Bioinformatic analysis reveals a binding site in RMST for miR-27a-3p. The direct association between RMST and miR-27a-3p is confirmed by dual luciferase reporter assay, RNA pull-down assay, and real time-quantitative polymerase chain reaction (RT-qPCR). miR-27a-3p is upregulated in CRC tumor specimens relative to normal specimens, and there is a negative correlation between RMST and miR-27a-3p in CRC tumor specimens. In addition, the effects of RMST overexpression are weakened by the elevation of miR-27a-3p. RMST and retinoid X receptor (RXRα) share the same complementary site with miR-27a-3p. The direct association between RXRα and miR-27a-3p is confirmed by RNA pull-down assay, RT-qPCR and western blot analysis. Overexpression of RMST induces RXRα expression and inactivates the Wnt signaling pathway by decreasing ß-catenin levels in CRC cells. Collectively, our findings reveal a pivotal role of RMST in regulating miR-27a-3p/RXRα axis and counteracting Wnt signaling pathway during the progression of CRC.
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Neoplasias Colorretais , MicroRNAs , RNA Longo não Codificante , Humanos , Linhagem Celular Tumoral , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Via de Sinalização WntRESUMO
BACKGROUND: Patients with prior illness are more vulnerable to heat stroke-induced injury, but the underlying mechanism is unknown. Recent studies suggested that NLRP3 inflammasome played an important role in the pathophysiology of heat stroke. METHODS: In this study, we used a classic animal heat stroke model. Prior infection was mimicked by using lipopolysaccharide (LPS) or lipoteichoic acid (LTA) injection before heat stroke (LPS/LTA 1 mg/kg). Mice survival analysis curve and core temperature (TC) elevation curve were produced. NLRP3 inflammasome activation was measured by using real-time PCR and Western blot. Mice hypothalamus was dissected and neuroinflammation level was measured. To further demonstrate the role of NLRP3 inflammasome, Nlrp3 knockout mice were used. In addition, IL-1ß neutralizing antibody was injected to test potential therapeutic effect on heat stroke. RESULTS: Prior infection simulated by LPS/LTA injection resulted in latent inflammation status presented by high levels of cytokines in peripheral serum. However, LPS/LTA failed to cause any change in animal survival rate or body temperature. In the absence of LPS/LTA, heat treatment induced heat stroke and animal death without significant systemic or neuroinflammation. Despite a decreased level of IL-1ß in hypothalamus, Nlrp3 knockout mice demonstrated no survival advantage under mere heat exposure. In animals with prior infection, their heat tolerance was severely impaired and NLRP3 inflammasome induced neuroinflammation was detected. The use of Nlrp3 knockout mice enhanced heat tolerance and alleviated heat stroke-induced death by reducing mice hypothalamus IL-1ß production with prior infection condition. Furthermore, IL-1ß neutralizing antibody injection significantly extended endotoxemic mice survival under heat stroke. CONCLUSIONS: Based on the above results, NLRP3/IL-1ß induced neuroinflammation might be an important mechanistic factor in heat stroke pathology, especially with prior infection. IL-1ß may serve as a biomarker for heat stroke severity and potential therapeutic method.
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Encéfalo/metabolismo , Encéfalo/patologia , Golpe de Calor/complicações , Golpe de Calor/fisiopatologia , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Doenças Neuroinflamatórias/complicações , Doenças Neuroinflamatórias/metabolismo , Animais , Anticorpos Neutralizantes/uso terapêutico , Modelos Animais de Doenças , Golpe de Calor/tratamento farmacológico , Golpe de Calor/patologia , Inflamassomos/metabolismo , Interleucina-1beta/imunologia , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/deficiência , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Transdução de Sinais , Ácidos Teicoicos , TermotolerânciaRESUMO
BACKGROUND & AIMS: Recent data on the coronavirus disease 2019 (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has begun to shine light on the impact of the disease on the liver. But no studies to date have systematically described liver test abnormalities in patients with COVID-19. We evaluated the clinical characteristics of COVID-19 in patients with abnormal liver test results. METHODS: Clinical records and laboratory results were obtained from 417 patients with laboratory-confirmed COVID-19 who were admitted to the only referral hospital in Shenzhen, China from January 11 to February 21, 2020 and followed up to March 7, 2020. Information on clinical features of patients with abnormal liver tests were collected for analysis. RESULTS: Of 417 patients with COVID-19, 318 (76.3%) had abnormal liver test results and 90 (21.5%) had liver injury during hospitalization. The presence of abnormal liver tests became more pronounced during hospitalization within 2 weeks, with 49 (23.4%), 31 (14.8%), 24 (11.5%) and 51 (24.4%) patients having alanine aminotransferase, aspartate aminotransferase, total bilirubin and gamma-glutamyl transferase levels elevated to more than 3× the upper limit of normal, respectively. Patients with abnormal liver tests of hepatocellular type or mixed type at admission had higher odds of progressing to severe disease (odds ratios [ORs] 2.73; 95% CI 1.19-6.3, and 4.44, 95% CI 1.93-10.23, respectively). The use of lopinavir/ritonavir was also found to lead to increased odds of liver injury (OR from 4.44 to 5.03, both p <0.01). CONCLUSION: Patients with abnormal liver tests were at higher risk of progressing to severe disease. The detrimental effects on liver injury mainly related to certain medications used during hospitalization, which should be monitored and evaluated frequently. LAY SUMMARY: Data on liver tests in patients with COVID-19 are scarce. We observed a high prevalence of liver test abnormalities and liver injury in 417 patients with COVID-19 admitted to our referral center, and the prevalence increased substantially during hospitalization. The presence of abnormal liver tests and liver injury were associated with the progression to severe pneumonia. The detrimental effects on liver injury were related to certain medications used during hospitalization, which warrants frequent monitoring and evaluation for these patients.
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Betacoronavirus , Infecções por Coronavirus/fisiopatologia , Testes de Função Hepática , Fígado/fisiopatologia , Pneumonia Viral/fisiopatologia , Adolescente , Adulto , Idoso , COVID-19 , Criança , China/epidemiologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Fígado/lesões , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/epidemiologia , Prevalência , SARS-CoV-2 , Fatores de Tempo , Adulto Jovem , Tratamento Farmacológico da COVID-19RESUMO
BACKGROUND: The clinical characteristics of novel coronavirus disease (COVID-2019) patients outside the epicenter of Hubei Province are less understood. METHODS: We analyzed the epidemiological and clinical features of all COVID-2019 cases in the only referral hospital in Shenzhen City, China, from January 11, 2020, to February 6, 2020, and followed until March 6, 2020. RESULTS: Among the 298 confirmed cases, 233 (81.5%) had been to Hubei, while 42 (14%) did not have a clear travel history. Only 218 (73.15%) cases had a fever as the initial symptom. Compared with the nonsevere cases, severe cases were associated with older age, those with underlying diseases, and higher levels of C-reactive protein, interleukin-6, and erythrocyte sedimentation rate. Slower clearance of the virus was associated with a higher risk of progression to critical condition. As of March 6, 2020, 268 (89.9%) patients were discharged and the overall case fatality ratio was 1.0%. CONCLUSIONS: In a designated hospital outside Hubei Province, COVID-2019 patients could be effectively managed by properly using the existing hospital system. Mortality may be lowered when cases are relatively mild, and there are sufficient medical resources to care and treat the disease.
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Betacoronavirus/genética , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Adolescente , Adulto , Fatores Etários , Antivirais/uso terapêutico , Sedimentação Sanguínea , Proteína C-Reativa/análise , COVID-19 , Criança , China/epidemiologia , Infecções por Coronavirus/sangue , Infecções por Coronavirus/tratamento farmacológico , Feminino , Hospitalização , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Resultado do Tratamento , Adulto Jovem , Tratamento Farmacológico da COVID-19RESUMO
MicroRNA (miRNA) exerts an important part in colon cancer cell proliferation and apoptosis. Meanwhile, the dysregulation of some miRNAs is detected in colon cancer cells. However, it remains unclear about the underlying mechanism of their effects on tumor pathogenesis. The current work aimed to examine the miR-1184 effect on colon cancer cells. The differentially expressed miRNAs (DEMs), including miR-9-3p, miR-1184, miR-492, miR-92a-1-5p and miR-20a-3p, were obtained from the GSE115108 and GSE132619 data sets using the 'GEO2R' online tool. Based on the findings, miR-1184 was significantly down-regulated within colon cancer cells and tissues. Moreover, the experimental results of CCK8, flow cytometry, colony formation and Western blotting assays showed that, miR-1184 over-expression suppressed colon cancer cell proliferation through inhibiting Ki67 expression and promoted their apoptosis through up-regulating cleaved caspase-3 and down-regulating Bcl-2 expression. By contrast, miR-1184 inhibition exerted the opposite effects. A total of 110 target genes of miR-1184 were predicted using the TargetScan and miRTarBase databases, which were then used to construct the protein-protein interaction (PPI) network based on the DAVID and STRING websites and to perform GO and KEGG pathway enrichment analyses. The MCODE plug-in of cytoscape was utilized to verify that CSNK2A1 was the target gene and key gene in significant modules. MiR-1184 directly targets CSNK2A1 via using RNA immunoprecipitation assay and luciferase reporter gene assay. According to the results, CSNK2A1 over-expression reversed the functions of miR-1184 over-expression in suppressing colon cancer cell proliferation and enhancing their apoptosis. In conclusion, over-expression of miR-1184 inhibits colon cancer cell proliferation but promotes their apoptosis through down-regulating CSNK2A1 expression.
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Neoplasias do Colo/genética , Regulação para Baixo , MicroRNAs/genética , Apoptose , Caseína Quinase II/genética , Linhagem Celular Tumoral , Proliferação de Células , Bases de Dados Genéticas , Feminino , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HT29 , Humanos , MasculinoRESUMO
Long noncoding RNAs (lncRNAs) are ubiquitous transcripts that play key roles in regulating gene expression at the levels of transcription, RNA processing, and translation. Aberrant expression and mutations of lncRNAs represent a driving force behind oncogenesis and development of tumours. However, most of the lncRNAs are still being undiscovered, and conclusive experimental evidence for their functional relevance continues to be lacking for most malignancies. We have found that lncRNA long intergenic non-protein-coding RNA 341 (LINC00341) is aberrantly downregulated by microarray-based screenings on nonmetastatic and metastatic colorectal carcinoma (CRC) specimens; LINC00341 is a novel long intergenic non-protein-coding RNA with unknown functions. LINC00341 overexpression restricts tumour growth and promotes its apoptosis. Instead, LINC00341 silencing accelerates CRC cell proliferation and migration. RNA-pulldown assay identifies LINC00341 physically binds to HMGB2 and stabilizes the localization of HMGB2 in the cytoplasm. Notably, LINC00341 knockdown leads to the shift of HMGB2 into nuclear, in which it triggers epithelial to mesenchymal transition (EMT) programming. Moreover, LINC00341 can also promote apoptosis. SIGNIFICANCE OF THE STUDY: LncRNAs are ubiquitous transcripts that play key roles in regulating gene expression at the levels of transcription, RNA processing, and translation. Aberrant expression and mutations of lncRNAs represent a driving force behind oncogenesis and development of tumours. However, the function of lncRNA still needs further exploration. Our study has revealed a new noncoding RNA-mediated regulatory network that highly likely protects colorectal carcinoma by preventing migration and apoptosis. The results will help further explore the molecular details about the progression of colorectal carcinoma and stimulate efforts to develop effective therapies.
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Apoptose/genética , Movimento Celular/genética , Neoplasias Colorretais/genética , Transição Epitelial-Mesenquimal , RNA Longo não Codificante/genética , Idoso , Biotinilação , Linhagem Celular Tumoral , Sobrevivência Celular , Colo/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Metástase Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos , Fenótipo , Prognóstico , Biossíntese de ProteínasRESUMO
Long noncoding RNAs (lncRNAs) have recently emerged as important biomarkers of cancer progression. Here, we proposed to develop a lncRNA-based signature with a prognostic value for colorectal cancer (CRC) overall survival (OS). Through mining microarray datasets, we analyzed the lncRNA expression profiles of 122 patients with CRC from Gene Expression Omnibus. Associations between lncRNA and CRC OS were firstly evaluated through univariate Cox regression analysis. A random survival forest method was applied for further screening of the lncRNA signature, which resulted in eight lncRNAs, including PEG3-AS1, LOC100505715, MINCR, DBH-AS1, LINC00664, FAM224A, LOC642852, and LINC00662. Combination of the eight lncRNAs weighted by their multivariate Cox regression coefficients formed a prognostic signature, through which, we could divide the 122 patients with CRC into two subgroups with significantly different OS. Good robustness of the lncRNA signature's prognostic value was verified through an independent data set consisting of 55 patients with CRC. In addition, gene set enrichment analysis indicated the potential association between high prognostic value and oxygen metabolism-related processes. This result should indicate that lncRNAs could be a useful signature for CRC prognosis.
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Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/biossíntese , RNA Neoplásico/biossíntese , Neoplasias Colorretais/genética , Intervalo Livre de Doença , Feminino , Humanos , Masculino , RNA Longo não Codificante/genética , RNA Neoplásico/genética , Taxa de SobrevidaRESUMO
Colorectal cancer (CRC) is the third most common cancer worldwide. This study aimed to explore the regulatory mechanisms of miRNAs in CRC. Differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) in CRC tissue samples compared with control samples in mRNA and miRNA datasets were screened. Functional and pathway enrichment analysis of the DEGs was carried out. Targets of the DEMs were identified. Overlaps between the DEGs and targets of DEMs were selected. The miRNA-mRNA regulatory network of these overlaps was constructed and visualized. The candidate genes selected were validated by quantitative real-time PCR. DEGs were identified and considered DEGs-1 and DEGs-2. A total of 584 genes in DEGs-1 and 527 genes in DEGs-2 were obtained, including 465 overlaps, and 44 DEMs were identified. The overlaps were enriched in 46 Gene Ontology terms and 19 Kyoto Encyclopedia of Genes and Genomes pathways. Moreover, 137 overlapped genes between targets of the DEMs and the 465 overlaps were obtained. The miRNA-mRNA regulating network of the 137 overlapped genes was constructed. Extracellular matrix-related proteins and pathways might play critical roles in the development of CRC. The quantitative real-time PCR results of the candidates were in agreement with the bioinformatics analysis. miR-128, miR-182, and miR-143 might be key miRNAs regulating cell proliferation and metastasis of CRC.
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Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , MicroRNAs/genética , RNA Mensageiro/metabolismo , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Prognóstico , RNA Mensageiro/genéticaRESUMO
Presently, various tissue engineering methods using adult stem cells and biomaterials are being confirmed to regenerate vessels, cardiac muscle, bladder, and intestines. However, there are few studies about the repair of the lower esophageal sphincter (LES) may help alleviate the symptoms of gastroesophageal reflux disease (GERD). This study aims to determine whether Adipose-Derived Stem Cells (ADSCs) combined with regenerated silk fibroin (RSF) solution could regenerate the LES. In vitro, the ADSCs were isolated, identified, and then cultured with an established smooth muscular induction system. In vivo, in the experimental groups, CM-Dil labeled ADSCs or induced ADSCs mixed with RSF solution were injected into the LES of rats after the development of the animal model of GERD respectively. The results showed that ADSCs could be induced into smooth muscular-like cells with the expression of h-caldesmon, calponin, α-smooth muscle actin, and a smooth muscle-myosin heavy chain in vitro. In vivo, the thickness of LES in the experiment rats was much thicker than those in the controlled groups. This result indicated that ADSCs mixed with RSF solution might contribute to the regeneration of the LES, thus reducing the occurrence of GERD.
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By influencing the type and quality of information that relay cells transmit, local interneurons in thalamus have a powerful impact on cortex. To define the sensory features that these inhibitory neurons encode, we mapped receptive fields of optogenetically identified cells in the murine dorsolateral geniculate nucleus. Although few in number, local interneurons had diverse types of receptive fields, like their counterpart relay cells. This result differs markedly from visual cortex, where inhibitory cells are typically less selective than excitatory cells. To explore how thalamic interneurons might converge on relay cells, we took a computational approach. Using an evolutionary algorithm to search through a library of interneuron models generated from our results, we show that aggregated output from different groups of local interneurons can simulate the inhibitory component of the relay cell's receptive field. Thus, our work provides proof-of-concept that groups of diverse interneurons can supply feature-specific inhibition to relay cells.
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BACKGROUND: Although uncommon during hepatobiliary-pancreatic (HBP) surgery, iatrogenic intraoperative injury to a major artery requires prompt and appropriate repair. Here, we outline our surgical experience with the repair of this injury and compare our experience to findings garnered from a selective review of the literature. METHODS: We retrospectively analyzed the clinical diagnoses, surgical methods, sites of arterial injury, operative repair, intra-operative blood loss, blood transfusion requirements, postoperative management and outcome of 17 consecutive patients who sustained iatrogenic intra-operative injuries to major arteries during HBP surgery between January 2008 and December 2013. RESULTS: Depending on the location and extent of injury, suture repair, primary end-to-end anastomosis, artery transposition, interposition grafting, or arterio-portal shunting were used. Postoperative morbidity occurred in three cases and there was only one case of in-hospital mortality (5.9%). No arterial thrombosis or other repair-related complications were found after the operation with a follow-up duration of 6 months. CONCLUSIONS: The use of an optimal repair method for injured arteries based on their location and extent resulted in a satisfactory outcome.
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Procedimentos Cirúrgicos do Sistema Digestório , Procedimentos Cirúrgicos Vasculares , Artérias/cirurgia , Humanos , Doença Iatrogênica/epidemiologia , Estudos RetrospectivosRESUMO
AIM: To develop an autophagy-gene-based signature that could help to anticipate the therapeutic effects of Colorectal Cancer (CRC). METHODS: We downloaded the gene expression profiles of CRC samples from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) datasets. Genes with significant prognostic value in CRC were screened through univariate Cox regression analysis, while the LASSO Cox regression method was applied to screen optimal genes to construct the autophagy-related prognostic signature. RESULTS: 11 autophagy genes were identified and selected for the establishment of prognosis prediction model for CRC patients. The CRC patients were classified into the low- and high-risk groups according to the optimal cutoff value. The time-dependent ROC curves indicated the good performance of this model in prognosis prediction, with AUC values of 0.66, 0.66, and 0.67 at 1, 3 and 5 years for TCGA samples, as well as AUC values of 0.63, 0.65 and 0.64 for GEO samples, respectively. The multivariate Cox regression analysis results confirmed risk score as the independent marker for prognosis prediction in CRC. Besides, the constructed nomogram also had high predictive value. The results analysis on the tumor infiltrating immune cells (TIICs) relative ratios and mRNA levels of key immune checkpoint receptors indicated the signature was closely related to immune microenvironment of CRC in the context of TIICs and immune checkpoint receptors' mRNA level. The proportion of MSI-L + MSI-H in the high-risk group was higher than that in the low-risk group. Moreover, the tumor purity was evaluated by estimate function package suggested that lower tumor purity in CRC might lead to a poorer prognosis. CONCLUSION: The autophagy-related features obtained in this study were able to divide the CRC patients into low- and high-risk groups, which should be contribute to the decision-making of CRC treatment.
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Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Biologia Computacional/métodos , Redes Reguladoras de Genes , Autofagia , Bases de Dados Genéticas , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Nomogramas , Prognóstico , Análise de Regressão , Análise de Sobrevida , Microambiente TumoralRESUMO
Objective: Our study aimed to construct a robust long non-coding RNA (lncRNA) prognostic signature for colorectal cancer (CRC) metastasis. Methods: Differentially expressed lncRNAs were identified between metastatic CRC and non-metastatic CRC samples from The Cancer Genome Atlas Database (TCGA) using the edgeR package. The differentially expressed lncRNAs with prognosis of patients with CRC metastasis were identified by univariate Cox regression analysis, followed by a stepwise multivariate Cox regression model. The survminer package in R was used to identify the optimal cutoff point for high-risk and low-risk groups. The receiver operating characteristic (ROC) curves were plotted to assess this signature. To explore potential signaling pathways associated with these lncRNAs, Gene Set Enrichment Analysis (GSEA) was performed. Results: A 6-lncRNA signature was built based on the lncRNA expression profile for CRC metastasis. The optimal cutoff value was used to classify high-risk and low-risk groups using the survminer package. The high-risk groups could have poorer survival time than the low-risk groups. ROC curve result indicated that this lncRNA signature had high sensitivity and accuracy. GSEA analysis results showed that the six lncRNAs were significantly enriched in several CRC metastasis-related signaling pathways such as "cell cycle," "DNA replication," "mismatch repair," "oxidative phosphorylation," "regulation of autophagy," and "insulin signaling pathway." Conclusion: Our study constructed a 6-lncRNA model for predicting the survival outcomes of patients with CRC metastasis, which could become potential prognostic biomarkers, and therapeutic targets for CRC metastasis.
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The aim of the present study was to screen colorectal cancer (CRC) tissue and adjacent tissue for differences in circular RNA (circRNA) expression, to analyze the related miRNAs and messenger RNAs (mRNAs), and to investigate the circRNA expression in CRC and its function. The circRNA expression profile was generated using CapitalBio microarray technology. The differentially expressed circRNAs were identified with GeneSpring 12.5 software. Subsequently, the related mRNAs of the differentially expressed circRNAs were annotated with the molecule annotation system (MAS) 3.0, and the diseases, pathways and functional enrichment analysis of these mRNAs were performed using the KEGG orthologybased annotation system (KOBAS) 3.0. In addition, the target miRNAs of differentially expressed circRNAs were screened using the miRanda algorithm. The circRNA/miRNA network was constructed for the top 8 most significant differentially expressed circRNAs with Cytoscape software 3.4.0. A total of 10,245 differentially expressed circRNAs were identified, including 6,264 upregulated ones, and 3,981 downregulated ones. The related mRNAs were enriched in 462 KEGG diseases, 411 FunDO, 669 NHGRI GWAS catalog, and 845 OMIM; and 1,334 Reactomes, 281 KEGG pathways, 117 PANTHER and 193 BioCyc; and 11,606 Gene Ontology (GO) terms. A total of 133 circRNA/miRNA pairs were involved in the circRNA/miRNA network. hsa_circ_0126897_CBC1 may be a potential biomarker for CRC, and the cell cycle was closely associated with the occurrence and development of CRC.
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Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Perfilação da Expressão Gênica/métodos , Análise de Sequência com Séries de Oligonucleotídeos/métodos , RNA/genética , Detecção Precoce de Câncer , Feminino , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Anotação de Sequência Molecular , RNA CircularRESUMO
MicroRNAs (miRNAs) are small noncoding RNAs, which are critical in a diverse range of biological processes, including development, differentiation, homeostasis, and in the formation of diseases by accelerating and/or inhibiting the translation of mRNAs. The present study aimed to examine the potential role of miRNA (miR)2055p in the developmental process of colorectal cancer (CRC) through proteintyrosine kinase 7 (PTK7). Initially, TargetScan was used to predict the miRNA target sites in the sequence of the PTK7 3'untranslated region. It was then found that the mRNA expression level of miR2055p was lower in CRC cells, determined using reverse transcriptionquantitative polymerase chain reaction analysis, and there was a negative correlation between miR2055p and PTK7 in CRC tissues. It was also found that miR2055p regulated the gene transcription of PTK7, determined using a luciferase reporter assay. The results of RTqPCR and western blot analyses in human colorectal cancer revealed that miR2055p suppressed the expression of PTK7. Finally, it was revealed that miR2055p restricted the proliferation ability of CRC cells through inhibiting PTK7, which was determined using colony forming and 3(4,5dimethylthiazol2yl)2,5diphenyltetrazolium bromide assays. miR2055p accelerated cell apoptosis through inhibiting PTK7, demonstrated using Annexin VFITC/propidium iodide staining. The results of a Transwell assay indicated that miR2055p inhibited the migration and invasion abilities of CRC cells through inhibiting PTK7. Therefore, miR2055p is involved in the proliferation, migration and invasion of CRC through inhibiting PTK7.
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Moléculas de Adesão Celular/biossíntese , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/metabolismo , MicroRNAs/metabolismo , Proteínas de Neoplasias/biossíntese , RNA Neoplásico/metabolismo , Receptores Proteína Tirosina Quinases/biossíntese , Moléculas de Adesão Celular/genética , Linhagem Celular Tumoral , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Humanos , MicroRNAs/genética , Invasividade Neoplásica , Proteínas de Neoplasias/genética , RNA Neoplásico/genética , Receptores Proteína Tirosina Quinases/genéticaRESUMO
The aim of the present study was to investigate the mechanism of metastasis in colorectal cancer (CRC) using microRNA (miRNA) and mRNA expression profiles. The mRNA and miRNA expression profiles of the GSE2509 and GSE56350 datasets were obtained from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified using the limma software package. The Database for Annotation, Visualization and Integrated Discovery was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEGs. The predicted target genes associated with the DEMs were identified using the miRWalk database and the enrichment analysis was conducted using the clusterProfiler package. The miRNA-gene molecular interaction network was visualized using the Cytoscape software platform. A total of 544 DEGs and 42 DEMs were identified. DEGs were annotated in 320 GO terms and 11 KEGG pathways. Overall, 366 miRNA-gene pairs were identified and the miRNA-gene network was visualized. Furthermore, the predicted target genes were mainly classified in 12 pathways. The results of the present study suggest that fibronectin type III domain-containing 3B, cysteine rich transmembrane BMP regulator 1 and forkhead box J2 may be potential therapeutic and prognostic targets of metastatic CRC. In addition, pathways in cancer, the Wnt signaling pathway and extracellular matrix-receptor interaction may play a critical role in CRC metastasis.
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The main limitation of liver transplantation as a treatment for end-stage liver disease or acute liver failure is the scarcity of liver organ donors. To develop an alternative therapy for acute liver failure, mesenchymal stem cell (MSC)-seeded regenerated silk fibroin (RSF) matrices were evaluated in vitro and in vivo. Adipose-derived mesenchymal stem cells (ADSCs) and bone marrow-derived mesenchymal stem cells (BMSCs) were planted and grown on RSF scaffolds to form a scaffold complex. The RSF-MSC scaffold complex (the experimental group) and neat RSF scaffolds (the control group) were then placed onto the liver surface of mice induced by CCl4 and detected after 5, 7, 14, 28, and 60 days. The growth and distribution of MSCs were tracked using fluorescence microscopy and live small animal fluorescence. Liver functions were tested using an automatic biochemistry analyzer. The histological kinetics of RSF complex and liver tissues were observed using hematoxylin & eosin staining. We found that MSCs exhibited good biocompatibility with RSF and differentiated to hepatocyte-like cells in vitro. Liver functions of the mice in the experimental group were significantly improved than that in the control group. Moreover, angiogenesis and hepatocyte-like cells were discovered in the RSF scaffolds in an animal model of acute liver failure on the fifth day and in the second month, respectively. The MSCs-RSF matrices show an obvious therapeutic ability for injured liver function of mice, which is more efficient than the neat RSF scaffolds.