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Bacterial adhesion plays a vital role in forming and shaping the structure of electroactive biofilms that are essential for the performance of bioelectrochemical systems (BESs). Type IV pili are known to mediate cell adhesion in many Gram-negative bacteria, but the mechanism of pili-mediated cell adhesion of Geobacter species on anode surface remains unclear. Herein, a minor pilin PilV2 was found to be essential for cell adhesion ability of Geobacter sulfurreducens since the lack of pilV2 gene depressed the cell adhesion capability by 81.2% in microplate and the anodic biofilm density by 23.1 % at -0.1 V and 37.7 % at -0.3 V in BESs. The less cohesiveness of mutant biofilms increased the charge transfer resistance and biofilm resistance, which correspondingly lowered current generation of the pilV2-deficient strain by up to 63.2 % compared with that of the wild-type strain in BESs. The deletion of pilV2 posed an insignificant effect on the production of extracellular polysaccharides, pili, extracellular cytochromes and electron shuttles that are involved in biofilm formation or extracellular electron transfer (EET) process. This study demonstrated the significance of pilV2 gene in cell adhesion and biofilm formation of G. sulfurreducens, as well as the importance of pili-mediated adhesion for EET of electroactive biofilm.
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Aderência Bacteriana , Biofilmes , Proteínas de Fímbrias , Geobacter , Geobacter/fisiologia , Geobacter/genética , Proteínas de Fímbrias/genética , Proteínas de Fímbrias/metabolismo , Fímbrias Bacterianas/fisiologia , Fímbrias Bacterianas/metabolismo , Fontes de Energia BioelétricaRESUMO
[This retracts the article DOI: 10.3892/ol.2018.8645.].
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Bioelectrochemical systems (BESs) are unique devices that harness the metabolic activity of electroactive microorganisms (EAMs) to convert chemical energy stored in organic substrates into electrical energy. Enhancing electron transfer efficiency between EAMs and electrodes is the key to practical implementation of BESs. Considering the role of outer membrane vesicles (OMVs) in mediating electron transfer of EAMs, a genetic engineering strategy to achieve OMVs overproduction was explored to enhance electron transfer efficiency and the underlying mechanisms were investigated. This study constructed a mutant strain of Geobacter sulfurreducens that lacked the ompA gene encoding an outer membrane protein. Experimental results showed that the mutant strain produced more OMVs and possessed higher electron transfer efficiency in Fe(III) reduction, dye degradation and current generation in BESs than the wild-type strain. More cargoes such as c-type cytochromes, functional proteins, eDNA, polysaccharides and signaling molecules that might be favorable for electron transfer and biofilm formation were found in OMVs produced by ompA-deficient anodic biofilm, which possibly contributed to the improved electron transfer efficiency of ompA-deficient biofilm. The results indicate that overproduction of OMVs in EAMs might be a potential strategy to enhance BESs performance.
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Técnicas Biossensoriais , Geobacter , Oxirredução , Compostos Férricos , Elétrons , Transporte de Elétrons , Geobacter/genéticaRESUMO
The basis for bioelectrochemical technology is the capability of electroactive bacteria (EAB) to perform bidirectional extracellular electron transfer (EET) with electrodes, i.e. outward- and inward-EET. Extracellular polymeric substances (EPS) surrounding EAB are the necessary media for EET, but the biochemical and molecular analysis of EPS of Geobacter biofilms on electrode surface is largely lacked. This study constructed Geobacter sulfurreducens-biofilms performing bidirectional EET to explore the bidirectional EET mechanisms through EPS characterization using electrochemical, spectroscopic fingerprinting and proteomic techniques. Results showed that the inward-EET required extracellular redox proteins with lower formal potentials relative to outward-EET. Comparing to the EPS extracted from anodic biofilm (A-EPS), the EPS extracted from cathodic biofilm (C-EPS) exhibited a lower redox activity, mainly due to a decrease of protein/polysaccharide ratio and α-helix content of proteins. Furthermore, less cytochromes and more tyrosine- and tryptophan-protein like substances were detected in C-EPS than in A-EPS, indicating a diminished role of cytochromes and a possible role of other redox proteins in inward-EET. Proteomic analysis identified a variety of redox proteins including cytochrome, iron-sulfur clusters-containing protein, flavoprotein and hydrogenase in EPS, which might serve as an extracellular redox network for bidirectional EET. Those redox proteins that were significantly stimulated in A-EPS and C-EPS might be essential for outward- and inward-EET and warranted further research. This work sheds light on the mechanism of bidirectional EET of G. sulfurreducens biofilms and has implications in improving the performance of bioelectrochemical technology.
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Matriz Extracelular de Substâncias Poliméricas , Geobacter , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Elétrons , Proteômica , Biofilmes , Oxirredução , Citocromos/metabolismoRESUMO
PURPOSE: In a phase IIb trial of nimotuzumab plus gemcitabine, substantial clinical benefits were observed in patients with locally advanced or metastatic pancreatic cancer (PC). Therefore, we conducted a phase III clinical study to verify the efficacy and safety of this combination regimen in patients with K-Ras wild-type tumors (ClinicalTrials.gov identifier: NCT02395016). PATIENTS AND METHODS: Eligible patients were randomly assigned to receive nimotuzumab (400 mg once per week) or placebo followed by gemcitabine (1,000 mg/m2 on days 1, 8, and 15, once every 4 weeks) until disease progression or unacceptable toxicity. The primary end point was overall survival (OS) and the secondary end points were progression-free survival (PFS), response rates, and safety. RESULTS: A total of 480 patients were screened; 92 patients were enrolled and 82 patients with K-Ras wild-type tumors were eligible. In the full analysis set, the median OS was 10.9 versus 8.5 months, while the restricted mean survival time (RMST) was 18.05 versus 11.14 months for the investigational versus control arm (ratio of control v investigation = 0.62 [0.40-0.97]; P = .036). Median PFS was 4.2 versus 3.6 months in the investigational versus control arm (log-rank P = .04; hazard ratio, 0.60 [0.37-0.99]) and the restricted mean PFS time was 8.08 versus 4.76 months (RMST ratio, 0.58 [0.38-0.90]; P = .036). Both OS and PFS were longer in the nimotuzumab group than in the placebo group. The objective response rates and disease control rates were 7% versus 10% and 68% versus 63% for the investigational and control groups, respectively. The incidence of adverse events were comparable between the two groups. CONCLUSION: In patients with locally advanced or metastatic K-Ras wild-type PC, nimotuzumab plus gemcitabine significantly improved OS and PFS with a good safety profile.
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Gencitabina , Neoplasias Pancreáticas , Humanos , Desoxicitidina , Anticorpos Monoclonais Humanizados/efeitos adversos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Progressão da Doença , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Environmental concentrations of antibiotics, usually below MIC, have significant biological effects on bacterial cells. Sub-MIC antibiotics exposure induces bacteria to produce outer membrane vesicles (OMVs). Recently, OMVs is discovered as a novel pathway for dissimilatory iron reducing bacteria (DIRB) to mediate extracellular electron transfer (EET). Whether and how the antibiotic-induced OMVs modulate iron oxides reduction by DIRB have not been studied. This study showed the sub-MIC antibiotics (ampicillin or ciprofloxacin) increased OMVs secretion in Geobacter sulfurreducens, and the antibiotic-induced OMVs contained more redox active cytochromes facilitating iron oxides reduction, especially for the ciprofloxacin-induced OMVs. Deduced from a combination of electron microscopy and proteomic analysis, the influence of ciprofloxacin on SOS response triggered prophage induction and led to the formation of outer-inner membrane vesicles (OIMVs) in, which was a first report in Geobacter species. While ampicillin disrupting cell membrane integrity resulted in more formation of classic OMVs from outer membrane blebbing. The results indicated that the different structure and composition of vesicles were responsible for the antibiotic-dependent regulation on iron oxides reduction. This newly identified regulation on EET-mediated redox reactions by sub-MIC antibiotics expands our knowledge about the impact of antibiotics on microbial processes or "non-target" organisms.
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Antibacterianos , Proteômica , Antibacterianos/toxicidade , Ciprofloxacina/farmacologia , Óxidos/metabolismo , Ampicilina/farmacologia , FerroRESUMO
Gastric cancer (GC) is a malignant tumor originating from the gastric epithelium, and its incidence and mortality rates rank third among all malignant tumors worldwide. It is also one of the most common cancers in China and is treated predominantly by Western medicine in clinical practice. However, with the advancements in medical technology and informatics, the values of traditional Chinese medicine (TCM) in preventing and treating GC and improving prognosis have increasingly been recognized. According to TCM, clinical manifestations of GC can be divided into Yege (dysphagia), regurgitation, stomach pain, and Zhengxia (abdominal mass). Due to the unbalanced distribution of health care resources in China, most GC patients already have progressive or advanced-stage disease at the first diagnosis. As a result, most GC patients have poor physical function, and surgery or chemotherapy alone will aggravate the impairment to the immune function and seriously affect the quality of life. In contrast, TCM therapies have shown promising efficacy in the management of these patients. Here we review the role of the integrated TCM and Western medicine in treating advanced GC.
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BACKGROUND: Treatment options for refractory metastatic colorectal cancer (mCRC) were limited. Anlotinib is a novel multitarget tyrosine kinase inhibitor. ALTER0703 study was conducted to assess efficacy and safety of anlotinib for patients with refractory mCRC. MATERIALS AND METHODS: This was a multicenter, double-blinded, placebo-controlled, randomized phase III trial involving 33 hospitals in China. Patients had taken at least two lines of therapies were 2:1 randomized to receive oral anlotinib (12 mg/day; days 1-14; 21 days per cycle) or placebo, plus best supportive care. Randomization was stratified by previous VEGF-targeting treatments and time from diagnosis to metastases. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL), and safety. RESULTS: A total of 419 patients (anlotinib: 282; placebo: 137) were treated from December 2014 to August 2016. The median PFS was improved in anlotinib group (4.1 months; 95% confidence interval [CI], 3.4-4.5) over placebo group (1.5 months; 95% CI, 1.4-1.5), with a hazard ratio (HR) of 0.34 (95% CI, 0.27-0.43; p < .0001). However, median OS was similar between two groups (8.6 months; 95% CI, 7.8-9.7 vs. 7.2 months; 95% CI, 6.2-8.8; HR, 1.02; p = .870). Improvements of ORR and DCR were observed in anlotinib over placebo. The most common grade ≥ 3 anlotinib related adverse events were hypertension (20.92%), increased γ-GT (7.09%), and hand-foot skin reaction (6.38%). CONCLUSION: Anlotinib was tolerated in Chinese patients with refractory mCRC. Although OS did not reach significant difference, anlotinib still provided clinical benefits by substantially prolonged PFS in these patients. IMPLICATIONS FOR PRACTICE: In this randomized clinical trial that included 419 patients with refractory metastatic colorectal cancer, substantial prolonged in progression-free survival was noted in patients who received anlotinib compared with those given placebo. Improvements on objective response rate and disease control rate was also observed in anlotinib group. However, overall survival was similar between the two groups. In a word, in third-line or above treatment of Chinese patients with refractory metastatic colorectal cancer, anlotinib provided clinical benefit by significantly prolonged progression-free survival.
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Neoplasias Colorretais , Quinolinas , Neoplasias Colorretais/tratamento farmacológico , Método Duplo-Cego , Humanos , Indóis , Qualidade de VidaRESUMO
Circular RNAs (circRNAs) are a class of novel endogenous transcripts with limited proteincoding abilities. CircRNAs have been demonstrated to function as critical regulators of tumor development and distant metastasis through binding to microRNAs (miRNAs) and interacting with RNAbinding proteins, thereby regulating transcription and translation. Emerging evidence has illustrated that certain circRNAs can serve as biomarkers for diagnosis and prognosis of cancer, and/or serve as potential therapeutic targets. Expression of functional circRNAs is commonly dysregulated in cancer and this is correlated with advanced TumorNodeMetastasis stage, lymph node status, distant metastasis, poor differentiation and shorter overall survival of cancer patients. Recently, an increasing number of studies have shown that circRNAs are closely associated with NSCLC. Functional experiments have revealed that circRNAs are intricately associated with the pathological progression of NSCLC. The present review provides an overview of the regulatory effect of circRNAs in the development and progression of NSCLC, taking into consideration various physiological and pathological processes, such as proliferation, apoptosis, invasion and migration, and their potential value as biomarkers and therapeutic targets.
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Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , RNA Circular/genética , Animais , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , RNA Circular/metabolismoRESUMO
The genus Cuscuta (Convolvulaceae) is an annual parasitic twining herb. There are about 200 species in this genus, which are widely distributed in tropical and subtropical areas. Cuscuta is mainly parasitic on crops bringing significant losses to the production of agriculture. Furthermore, dried seeds of C. chinensis and C. australis are used as a Chinese traditional herbal medicine. Despite the importance of Cuscuta species, it is difficult to distinguish these plants by the naked eye. Moreover, plastid sequence information available for Cuscuta species is limited. In this study, the complete chloroplast (cp) genome sequence of C. australis was determined using next-generation sequencing. The entire cp genome was determined to be 85,263 bp in length. It contained large single-copy (LSC) and small single-copy (SSC) regions of 50,384 and 6727 bp, respectively, which were separated by a pair of 14,076 bp inverted repeat (IR) regions. The genome contained 98 genes, including 61 protein-coding genes, 29 tRNA genes, and 4 rRNA genes. The overall GC content of the genome is 37.8%. A phylogenetic tree reconstructed by 26 chloroplast genomes reveals that C. australis is most related with Cuscuta pentagona in Convolvulaceae, with bootstrap support values of 100%.
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Exogenous electron mediators (EMs) can facilitate extracellular electron transfer (EET) via electron shuttling processes, but it is still unclear whether and how biofilm formation is affected by the presence of EMs. Here, the impacts of EMs on EET and biofilm formation were investigated in bioelectrochemical systems (BESs) with Shewanella oneidensis MR-1, and the results showed that the presence of five different EMs led to high density current production. All the EMs substantially promoted biofilm formation with 15-36 times higher total biofilm DNA with EMs than without EMs, and they also increased the production of extracellular polymeric substances, which was favorable for biofilm formation. The current decreased substantially after removing EMs from the medium or by replacing electrodes without biofilm, suggesting that both biofilm and EMs are required for high density current production. EET-related gene expression was upregulated with EMs, resulting in the high flux of cell electron output. A synergistic mechanism was proposed: EMs in suspension were quickly reduced by the cells and reoxidized rapidly by the electrode, resulting in a microenvironment with sufficient oxidized EMs for biofilm formation, and thus, besides the well-known electron shuttling process, the EM-induced high biofilm formation and high Mtr gene expression could jointly contribute to the EET and subsequently produce a high density current. This study provides a new insight into EM-enhanced current production via regulating the biofilm formation and EET-related gene expression.
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Fontes de Energia Bioelétrica , Shewanella , Biofilmes , Eletrodos , Transporte de Elétrons , Elétrons , Shewanella/genéticaRESUMO
Increasing evidences demonstrate that circular RNAs (circRNAs) are extensively implicated in various cancers including colorectal cancer (CRC). In the present study, we found that circRNA HIPK3 (circPIK3) was upregulated in CRC. We identified that circHIPK3 was closely related with unfavorable clinicopathological features in patients with CRC. Functional transwell assay and proliferation assay indicated that circHIPK3 served as an oncogene and promoted CRC cells migration, invasion and proliferation. Meanwhile, we found that formin like 2 (FMNL2) was a key downstream molecule in circHIPK3-induced metastasis and proliferation in CRC cells. We further verified that circHIPK3 was mainly located at cytoplasm through an immunofluorescence assay. An online bioinformatics screening and a GEO datasets analysis showed that microRNA 1207-5p (miR-1207-5p) was downregulated in CRC. Also, we found that miR-1207-5p shared a similar miR-1207-5p response elements (MREs-1207-5p). Meanwhile, we showed that miR-1207-5p suppressed CRC cells migration, invasion and proliferation via directly targeting of FMNL2. Even further, via a constructed luciferase assay, we indicated that circHIPK3 was another target of miR-1207-5p. Functionally, we proved that circHIPK3 enhanced FMNL2 mediated promotion of migration, invasion and proliferation by sponging of miR-1207-5p in CRC cells. In summary, the outcomes of this study illustrated that circHIPK3 promoted CRC cells migration, invasion and proliferation modulating of FMNL2 by sponging of miR-1207-5p. Our findings indicated that circHIPK3/miR-1207-5p/FMNL2 axis might be a new strategy in molecular treatment of CRC.
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Neoplasias Colorretais/genética , Forminas/genética , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/genética , MicroRNAs/genética , Proteínas Serina-Treonina Quinases/genética , RNA Circular/genética , Idoso , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Forminas/antagonistas & inibidores , Forminas/metabolismo , Células HT29 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Metástase Linfática , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , RNA Circular/antagonistas & inibidores , RNA Circular/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Análise de SobrevidaRESUMO
In recent years, extensive reports have been published concerning the molecular mechanism underlying the occurrence and progression of colorectal cancer. Circular RNAs (circRNAs) have been identified as important modulators in the biological processes of colorectal cancer. Microarray analysis unveiled that differential circ-0004277 expression was identified in tissue samples of colorectal cancer. High circ-0004277 expression was then verified in tissue samples and cell lines of colorectal cancer via qRT-PCR. Kaplan-Meier analysis was used for identifying the association between circ-0004277 expression and the overall survival rate of colorectal cancer patients. A relationship existed between higher circ-0004277 expression and decreased overall survival rate of colorectal cancer patients. From a functional perspective, circ-0004277 knockdown accelerated cell apoptosis and restrained cell proliferation of colorectal cancer. From mechanistic perspective, circ-0004277 upregulated PTMA by sponging miR-512-5p. Rescue assay was used for verifying the roles of the circ-0004277-miR-512-5p-PTMA axis. Both miR-512-5p and PTMA participated in circ-0004277-mediated colorectal cancer cell proliferation based on experiments. In summary, our study showed that circ-0004277 promoted the proliferation of colorectal cancer cells as a miR-512-5p sponge to upregulate the PTMA expression.
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Background and aim: Lung squamous cell carcinoma (LUSC), is a pathological subtype of lung cancer, accounting for 30% of the lung cancers. A reliable model was constructed, based on the whole gene expression profiles, to predict the prognosis of patients with LUSC. Methods: The RNA-Seq data of LUSC was downloaded from the TCGA database, and differentially expressed genes (p<0.05, |log2fold change| >1) were screened out. By univariate and multivariate Cox regression analysis, we identified seven prognosis-related genes. Then, we established a risk score staging system to predict the prognosis of patients with LUSC. Compared with other clinical parameters, the risk score was an independent prognostic factor and had a better performance in predicting prognosis. Finally, GSEA analysis was carried out to determine the enrichment pathway significantly. The risk score models were established by Cox proportional hazard regression analysis; the ROC curve was applied to test the performance of risk score model. All the statistical analysis was accomplished by R packages. Results: In this study, a model was constructed to predict prognosis, which contains seven genes: CSRNP1, CLEC18B, MIR27A, AC130456.4, DEFA6, ARL14EPL, and ZFP42. Based on the model, the risk score of each patient was calculated with LUSC (hazard ratio [HR]=2.673, 95% CI=1.871-3.525). It was found that the risk score can distinguish high-risk and low-risk groups in prognosis of LUSC patients, independently. Furthermore, the model was validated by ROC curves in the testing dataset and the whole dataset. Lastly, by gene set enrichment analysis (GSEA), we showed the main enrichment pathways were DNA damage stimulus, DNA repair, and DNA replication. It was suggested that the risk score may provide a new and reliable method for prognosis prediction. Conclusion: The results of this study suggested that the risk score based on seven-genes could indicate a promising and independent prognostic biomarker for LUSC patients.
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Circular RNAs (circRNAs) are a class of covalently closed non-coding RNAs and are widely involved in various cancers including colorectal cancer (CRC). Circular RNA PVT1 (circPVT1) was reported in several malignancies but the role it plays in CRC remains unclear. In our current research, we focused on the expression and function of circPVT1) works in CRC. We found that circPVT1 was upregulated in CRC. Also, we illustrated that the upregulated circPVT1 was closely correlated with poor prognosis and bad clinicopathological features of patients with CRC. Through a loss of function experiment, we showed that a downregulation of circPVT1 suppressed CRC cells metastasis. Through online prediction, we found that circPVT1 had a microRNA response element (MRE) for miR-145. Additionally, we demonstrated that miR-145 was downregulated in CRC. Even further, we showed that miR-145 was involved in circPVT1 mediated facilitation of CRC metastasis. In a further mechanical study, we demonstrated that circPVT1 could target miR-145. Lastly, we revealed that the metastasis-promoting role of circPVT1 in CRC was partially achieved via miR-145 sponging. In brief, the findings of the present study illustrated that circPVT1, working as an oncogene, promotes metastasis via miR-145 sponging in CRC. CircPVT1/miR-145 axial might be a novel point in targeting treatment of CRC.
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Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Invasividade Neoplásica/genética , RNA Circular/genética , Linhagem Celular Tumoral , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Prognóstico , Regulação para CimaRESUMO
Long non-coding RNAs (lncRNAs) are extensively involved in multiple malignancies including colorectal cancer (CRC). In the present study, we found a novel lncRNA, long intergenic non-protein coding RNA 483 (LINC00483), which was upregulated in CRC. We also illustrated that upregulated LINC00483 was correlated with poor clinicopathological features of patients with CRC. Functionally, we displayed that a knockdown of LINC00483 suppressed LOVO and HT29â¯cells proliferation and metastatic ability. We further illustrated that miR-204-3p was involved in LINC00483 induced proliferation and metastasis. An overexpression of miR-204-3p could attenuate the facilitative effect which LINC00483 presented. Through a luciferase assay, we showed the direct binding effect between LINC00483 and miR-204-3p. Even further, we revealed that LINC00483 and formin like 2 (FMNL2) shared a similar miR-204-3p response elements (MREs-204-3p). FMNL2 was a direct target of miR-204-3p. FMNL2 was a downstream gene of LINC00483 and participated in LINC00483 mediated proliferation and metastasis. Lastly, we proved that LINC00483 promoted proliferation and metastasis via modulating of FMNL2 in LOVO and HT29â¯cells. In summary, the outcomes of this study illustrated that LINC00483 promoted CRC cells proliferation and metastasis via modulating of FMNL2 by acting as a ceRNA of miR-204-3p. LINC00483/miR-204-3p/FMNL2 axial might be a novel target in molecular treatment of CRC.
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Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , MicroRNAs/genética , Proteínas/genética , RNA Longo não Codificante/genética , Adulto , Idoso , Sequência de Bases , Sítios de Ligação , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Forminas , Genes Reporter , Células HT29 , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Luciferases/genética , Luciferases/metabolismo , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Oligorribonucleotídeos Antissenso/genética , Oligorribonucleotídeos Antissenso/metabolismo , Prognóstico , Proteínas/metabolismo , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Análise de SobrevidaRESUMO
BACKGROUND: Compelling studies have demonstrated the correlation between aberrant expressed lncRNAs and human cancers, and revealed promise of these lncRNAs as biomarkers in predicting patients' survival and outcome. METHODS: We downloaded the RNA-seq data from the Cancer Genome Atlas, and screened out DEGs and DELs between gastric cancer tissues and normal gastric tissues. By bioinformatics analysis, we identified CTD-2510F5.4 was a malignant phenotype associated lncRNA. The expression levels of CTD-2510F5.4 in tissues were detected by ISH, and the relationships between CTD-2510F5.4 expression and clinicopathological characteristics were analyzed by statistical analysis. RESULTS: By bioinformatics analysis and functional analysis, we identified CTD-2510F5.4 was a malignant phenotype associated lncRNA of gastric cancer that potentially regulated cell cycle and apoptosis. CTD-2510F5.4 expression was significantly higher in gastric cancers, and was correlated with pathological grade, vascular or nerve invasion, AJCC TNM stage and OS. Moreover, gastric cancer patients with high CTD-2510F5.4 expression showed significantly shorter MST. High CTD-2510F5.4 expression was a independent risk factor for gastric cancers at pathological grade < III and without vascular or nerve invasion. CONCLUSIONS: We identified CTD-2510F5.4 was a malignant phenotype associated lncRNA potentially involved in the pathogenesis of gastric cancer. Our data also supported the clinical potential of CTD-2510F5.4 being a diagnostic and prognostic biomarker for gastric cancer.
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Adenocarcinoma/secundário , Biomarcadores Tumorais/genética , Carcinoma de Células em Anel de Sinete/secundário , RNA Longo não Codificante/genética , Neoplasias Gástricas/patologia , Adenocarcinoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose , Carcinoma de Células em Anel de Sinete/genética , Ciclo Celular , Sobrevivência Celular , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/genética , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
AIM: In this study, we aim to use bioinformatics approach to identify paclitaxel-targeted modulators potentially involved in the process of reversing the trastuzumab resistance. Materials & methods: We extracted data from GSE77346 to identify potential trastuzumab resistance-related genes, used bioinformatics analysis and functional/activity network approach to find genes involved in trastuzumab resistance reversal. RESULTS: We identified hub differentially expressed genes related to trastuzumab resistance, trastuzumab targeting and paclitaxel targeting, respectively. We then found C-Jun may be critical in trastuzumab resistance reversal. This process may involve transcriptional activation of DUSP1 by JUN, which lead to regulation of DUSP1-related signaling pathways. CONCLUSION: The present study revealed paclitaxel may reverse the trastuzumab resistance by JUN, which possibly in turn regulated DUSP1 and DUSP1-related signaling pathways.
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Antineoplásicos Fitogênicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Paclitaxel/farmacologia , Proteínas Proto-Oncogênicas c-jun/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Fosfatase 1 de Especificidade Dupla/genética , Fosfatase 1 de Especificidade Dupla/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Paclitaxel/uso terapêutico , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/efeitos dos fármacos , Receptor ErbB-2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Trastuzumab/farmacologia , Trastuzumab/uso terapêuticoRESUMO
Noncoding RNAs regulate the initiation and progression of osteosarcoma (OS). The role of long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) playing in OS and whether the function it working out was achieved through HDAC4 pathway remain uncovered. In this study, we illustrated that MALAT1 was upregulated and was correlated with poor prognosis in OS patients. Meanwhile, we demonstrated that a depression of MALAT1 suppressed proliferation and promoted apoptosis in OS cell line HOS and 143B. Further, we verified that MALAT1 exerting its function via upregulating of histone deacetylase 4 (HDAC4). Through an online prediction, a series of luciferase assays and RNA pull-down assays, we demonstrated that both MALAT1 and HDAC4 were the targets of microRNA-140-5p (miR-140-5p) via sharing a similar microRNA responding elements. Even further, we revealed that MALAT1 served as a ceRNA of HDAC4 via decoying of miR-140-5p. Finally, we proved that MALAT1 promoted OS tumor growth in an in vivo animal study. In summary, the outcomes of this study demonstrated the complex ceRNA network among MALAT, miR-140-5p, and HDAC4-mediated proliferation and apoptosis in OS. This study might provide a new axial in molecular treatment of OS.