RESUMO
Colorectal cancer (CRC) is a heterogeneous disease of the intestinal epithelium and ranks the third largest diagnosed malignancy in the world. Many studies have shown that the high risk of CRC is believed to be related to the formation of biofilms. To prove causation, it will be significant to decipher which specific bacteria in biofilms initiate and maintain CRC and fully describe their underlying mechanisms. Here we introduce a bacterial driver-passenger model. This model added a novel and compelling angle to the role of microorganisms, putting more emphasis on the transformation of bacterial composition in biofilms which play different roles in the development of CRC. In this model, bacterial drivers can initiate the formation of CRC through genotoxicity, while bacterial passengers maintain the CRC process through metabolites. On the basis of these pathogens, we further turned our attention to strategies that can inhibit and eradicate these pathogenic biofilms, with the aim of finding new ways to hinder colorectal carcinogenesis.
Assuntos
Neoplasias Colorretais , Microbioma Gastrointestinal , Bactérias , Biofilmes , Carcinogênese/patologia , Neoplasias Colorretais/patologia , HumanosRESUMO
PURPOSE: Our study aimed to explore the programmed death 1 (PD-1) expression on tumor-associated macrophage (TAM) in T cell non-Hodgkin lymphoma (T-NHL) and its relationship with lymphoma prognosis. The effect of PD-1 expression on the function of macrophages was also studied. METHODS: Multispectral image quantitative analysis was applied for detecting PD-1 expression on macrophages in T cell lymphoma tissues. The Kaplan-Meier analysis was performed to evaluate the value of PD-1 expression of TAM in predicting the overall survival of T-NHL. PD-1 overexpression THP-1-derived macrophage was constructed and was cocultured with Jurkat cells to explore the effect of PD-1 on macrophage function. RESULTS: In 17 T cell lymphoma cases, the 1-year overall survival rate was significantly lower in patients with higher PD-1 expression on TAMs (0.25 vs 0.86, p < 0.05). After co-cultured with Jurkat cells, classically activated (M1)-related markers on PD-1 overexpressed macrophages were significantly lower than those on controls, while the expressions of alternatively activated (M2) related markers were similar. The PD-1 overexpressed macrophages showed inhibited phagocytosis (4.42% vs 40.7%, p < 0.001) and increased IL-10 secretion (144.48 pg/ml vs 32.32 pg/ml, p < 0.001). CONCLUSION: High PD-1 expression on TAMs in T-NHL may predict poor prognosis. The PD-1 overexpression of macrophages significantly inhibited polarization of M1 macrophages and phagocytosis, and more IL-10 was excreted. These changes may enhance the pro-tumor effects of tumor microenvironment.
Assuntos
Linfoma de Células T/metabolismo , Receptor de Morte Celular Programada 1/biossíntese , Macrófagos Associados a Tumor/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Células Tumorais CultivadasRESUMO
PURPOSE: The current study aims to explore the effects of CDKN2A on cell proliferation and cycle, and investigate the underlying mechanisms. METHODS: Expression of CDKN2A in cervical cancer cell lines was evaluated by real-time quantitative PCR (RT-qPCR) and western blotting. Apoptotic rate was detected by Annexin V assay. MTT assay, Transwell assay and cell cycle assay kit were applied to examine the effect of CDKN2A on cell viability, invasion and cell cycle. Co-immunoprecipitation and western blotting were devoted to explore the mechanism by which CDKN2A contributes to cell function. RESULTS: CDKN2A was expressed at a low level in cervical cancer cell lines. Overexpression of CDKN2A inhibited cell proliferation and invasion, and caused cell cycle arrest in the G1 phase. CDKN2A mediates the AKT-mTOR signaling pathway by suppressing lactate dehydrogenase (LDHA). Taken together, our data revealed that CDKN2A can be applied as a therapeutic target for the treatment of cervical cancer in future. CONCLUSIONS: CDKN2A inhibits cell proliferation and invasion in cervical cancer through LDHA-mediated AKT-mTOR pathway.
Assuntos
Proliferação de Células/fisiologia , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , L-Lactato Desidrogenase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Neoplasias do Colo do Útero/metabolismo , Apoptose/fisiologia , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Regulação para Baixo/fisiologia , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular , Células HeLa , Humanos , Imunoprecipitação , Invasividade Neoplásica , Neoplasias do Colo do Útero/patologiaRESUMO
PURPOSE: Cetuximab (CTX) has been used to treat metastatic colorectal cancer (mCRC) with wild-type (wt) RAS and BRAF genes. Meanwhile HER2 amplification reportedly denoted CTX-resistant mCRC tumors. We investigated whether monitoring of HER2 amplification in circulating DNA allowed early detection of mCRC progression and CTX resistance. METHODS: We analyzed HER2 amplification in circulating DNA at 8-week intervals using ddPCR from 36 patients with RASwt/BRAFwt mCRC, who progressed after CTX treatments between July 2015 and January 2018. RESULTS: Of the 36 patients, 5 (13.9%) exhibited dynamic fluctuations of HER2 amplification in plasma in the course of CTX treatment, of whom 2 were positive for HER2 amplification in matched tumor specimens at baseline (per FISH). All 5 primary sites were left side: 3 rectums and 2 descending colon. HER2 ratio fluctuations in circulating DNA not only reflected changes in tumor volume, but their obvious increases presaged CT-documented progress by an average lead time of 2 months. Interestingly, progression-free survival did not significantly differ between these 5 patients and those without HER2 amplification (HR 1.06, 95% CI 0.40-2.77, P = 0.909). CONCLUSION: Plasma HER2 amplification detected by ddPCR changed over time and predicted resistance to CTX, by an average lead time of 2 months. Further study is needed to validate our findings.
Assuntos
Ácidos Nucleicos Livres/sangue , Cetuximab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Receptor ErbB-2/genética , Adulto , Idoso , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Amplificação de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Receptor ErbB-2/metabolismo , Resultado do TratamentoRESUMO
Circulating tumor cells (CTCs), as cells shed from solid tumor into the vasculature, play a significant role in tumor metastasis. In the peripheral blood, immune cells and stromal cells can interact with CTCs and influence their biological behaviors of survival, proliferation, dissemination, and immune evasion. These peripheral blood cells can evolve synergistically with CTCs to constitute the liquid microenvironment which is essential for tumor progression. Here, we review the mechanisms of peripheral blood cells interacting with CTCs and uncover their effects on both CTCs and tumor metastasis. Then, we introduce the applications of these CTC-associated peripheral blood cells in the clinical setting. Besides, some peripheral blood cell subsets are of additional clinical values to CTCs in cancer diagnosis and prognosis. To improve the clinical utility of CTCs, an integrative analysis of CTCs and associated peripheral blood cells should be advocated for, which could provide a novel insight into tumor biology and offer comprehensive information in cancer diagnosis, prognosis, and therapy efficacy evaluation.
Assuntos
Biomarcadores Tumorais/sangue , Células Sanguíneas/patologia , Neoplasias/diagnóstico , Células Neoplásicas Circulantes/patologia , Microambiente Tumoral , Humanos , Biópsia Líquida , Neoplasias/sangue , PrognósticoRESUMO
Circular RNAs (CircRNAs) are a type of non-coding RNAs (NcRNAs) with a closed annular structure. Until next-generation sequencing (NGS) is developed, the misunderstanding of circRNAs 'splicing error' has changed, and the mysterious veil of circRNAs has been revealed. NGS provides an approach to investigate circRNAs. Many scholars point out that circRNAs may play an important role in many diseases, especially cancer. At the same time, exosomes, as a kind of extracellular vesicles loaded with many contents, are a hotspot in recent years. They can act as 'messengers' between cells, especially in cancer. Lately, it is interesting circRNAs are enriched and stable in exosomes, also called exo-circRNAs, and there have been several articles on circRNAs associated with exosomes. In this review, we summarize the characteristics of circRNAs, especially its main functions. Then, we briefly introduce exosomes and their function in cancer. Finally, the known relation between circRNAs and exosomes is discussed. With further researches, exo-circRNAs may be a novel pathway for cancer diagnosis and targeted therapy.
Assuntos
Exossomos/fisiologia , Neoplasias/genética , RNA/fisiologia , Humanos , Sistema Imunitário/fisiologia , MicroRNAs/fisiologia , Metástase Neoplásica , RNA CircularRESUMO
Newcastle disease is a highly contagious disease responsible for major outbreaks and considerable economic losses in the poultry industry in China. There is still little information available regarding gene characterization of the NDV, especially in ducks and pigeons. Therefore, the aim of this study was to investigate NDV isolated from ducks and pigeons in Hubei, China. In this study, three NDVs from ducks and pigeons were isolated between 2013 and 2015.The fusion protein (F) gene of the NDV isolates was sequenced and phylogenetically analyzed. The clinical signs and gross histopathological lesions were examined. Phylogenetic analysis of these strains indicated that all the sequences are classified as genotype II. The isolates shared a 112 G-R-Q-G-R-L 117motif at the F protein cleavage site, indicating that these three isolates strains are lentogenic. Necropsy and histopathology showed the typical pathological changes. It was concluded that commercial ducks and pigeons in Hubei province carry lentogenic NDV strains with regular genetic divergence, indicating that these species may act as the main reservoirs of NDV in poultry. Therefore, strategies and surveillance should be undertaken to reduce the risk of ND outbreaks.
Assuntos
Animais , Columbidae/genética , Columbidae/virologia , Patos/genética , Patos/virologia , Vírus da Doença de Newcastle/classificação , Vírus da Doença de Newcastle/genéticaRESUMO
PURPOSE: Transcatheter arterial embolization (TAE) has been widely used in treating non-curative hepatocellular carcinoma (HCC). However, it is noticed that TAE may cause invasion of some cancer cells into circulation, resulting in distal metastasis and poor therapeutic outcome. Here, we aimed to reduce the side effects of TAE using the inhibitors for epidermal growth factor receptor (EGFR). METHODS: Transient hepatic artery ligation (HAL) was used as a mouse model for TAE. EGFR inhibitors were applied. Tumor size, presence of tumor cells in circulation, distal tumor formation, and activation of genes associated with tumor cell invasion and metastasis were analyzed. RESULTS: Inhibitors for EGFR significantly reduced the size of primary tumor, presence of tumor cells in circulation, and distal tumor formation after HAL. Further studies showed that EGFR inhibition suppressed several genes associated with tumor cell invasion and metastasis, such as vascular endothelial growth factor-A, stromal cell-derived factor 1, and Slug. CONCLUSION: EGFR inhibitor application may reduce circulating cancer cells during TAE and thus improve the therapy for advanced HCC.
Assuntos
Carcinoma Hepatocelular/patologia , Embolização Terapêutica/efeitos adversos , Receptores ErbB/antagonistas & inibidores , Neoplasias Hepáticas/patologia , Células Neoplásicas Circulantes/efeitos dos fármacos , Animais , Antineoplásicos Imunológicos/farmacologia , Cetuximab/farmacologia , Células Hep G2 , Humanos , Masculino , Camundongos , Camundongos Nus , Células Neoplásicas Circulantes/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
PURPOSE: Aspirin could reduce the risk of cancer metastasis. Circulating tumor cells (CTCs) are a key factor of cancer metastasis, but no evidence has revealed how aspirin affects CTCs and its epithelial-mesenchymal transition (EMT). Here, we conducted a clinical trial to investigate how aspirin affects CTCs in metastatic colorectal cancer (MCC) and breast cancer patients (MBC). METHODS: The trial is retrospective registered at clinicaltrials.gov (NCT02602938). The eligible patients are given 100 mg aspirin q.d. for 8 weeks, and CTCs are evaluated at baseline, 4 and 8 weeks for absolute number, phenotype (epithelial type, E+, mesenchymal type, M+, and biophenotypic type, B+), and vimentin expression. RESULTS: Data on 21 MCC and 19 MBC patients are analyzed, and it revealed that the CTC numbers decreased with aspirin treatment in MCC (p < 0.001) but not MBC (p = 0.0532); besides, ratio of E+ CTCs increased (p = 0.037) and M+ CTCs decreased at 2 months in MCC (p = 0.013), but neither the ratio of E+ or M+ CTCs changes significantly in MBC; vimentin expression of M+ CTCs is higher than E+ and B+ CTCs either in MBC or MCC patients at baseline (p < 0.01); and aspirin suppresses the vimentin expression in M+ (p = 0.002)and B+ (p = 0.006) CTCs of MCC and M+ CTCs of MBC (p = 0.004); besides it find vimentin expression in B+ (p = 0.004) or M+ (p < 0.001), CTCs are markedly decreased in patients with total CTC numbers declined. CONCLUSION: Aspirin could decrease CTCs numbers and block EMT transition in MCC patients and part of MBC patients.
Assuntos
Aspirina/administração & dosagem , Neoplasias da Mama/patologia , Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Células Neoplásicas Circulantes/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/administração & dosagem , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Neoplasias Colorretais/sangue , Neoplasias Colorretais/tratamento farmacológico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Células Neoplásicas Circulantes/efeitos dos fármacos , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Vimentina/metabolismo , Adulto JovemRESUMO
The aim of this study was to determine the proliferation and osteogenic activity of fibroblasts induced with fibronectin and their possible dose-dependent relationship. The fibroblasts obtained by tissue explants adherent method were induced with fibronectin at different concentrations of 0, 10, 20, 40, 60, and 80 µg/mL for 14 days. The 3H-thymidine and 3H-proline incorporation test was used to evaluate the synthesis of DNA and collagen by fibroblasts, respectively. The mineralized nodules and osteocalcin secretion, as vital osteogenic indicators, were detected with tetracycline labeling and 125I-labeled competitive immunoassay, respectively. Fibronectin significantly increased the synthesis of DNA and collagen by fibroblasts, especially at the concentration of 40 µg/mL (P<0.05). The increased secretion of osteocalcin in the supernatant was also statistically significant at the concentration of 40 µg/mL (P<0.05). The mineralized nodules with trabecula-like structure derived from induced fibroblasts were positive for tetracycline labeling. The granulation tissue-derived fibroblasts induced with fibronectin exhibited increased proliferative, functional and osteogenic potential. Fibroblasts are considered a possible in situ stem cell in tissue engineering.
Assuntos
Proliferação de Células/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibronectinas/farmacologia , Osteogênese/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Fibroblastos/fisiologia , Humanos , CoelhosRESUMO
This meta-analysis compared the efficacy and safety of the contact force (CF)-sensing catheter and second-generation cryoballoon (CB) ablation for treating atrial fibrillation (AF). Six controlled clinical trials comparing ablation for AF using a CF-sensing catheter or second-generation CB were identified from PubMed, EMBASE, Cochrane Library, Wanfang Data, and China National Knowledge Infrastructure. The procedure duration was significantly lower in the CB group compared with that in the CF group [mean difference (MD)=29.4; 95%CI=17.84-40.96; P=0.01], whereas there was no difference between the groups for fluoroscopy duration (MD=0.59; 95%CI=-4.48-5.66; P=0.82). Moreover, there was no difference in the incidence of non-lethal complications (embolic event, tamponade, femoral/subclavian hematoma, arteriovenous fistula, pulmonary vein stenosis, phrenic nerve palsy, and esophageal injury) between the CB and the CF groups (8.38 vs 5.35%; RR=0.66; 95%CI=0.37-1.17; P=0.15). Transient phrenic nerve palsy occurred in 17 of 326 patients (5.2%) of the CB group vs none in the CF group (RR=0.12; 95%CI=0.03-0.43; P=0.001). A comparable proportion of patients in CF and CB groups suffered from AF recurrence during the 12-month follow-up after a single ablation procedure [risk ratio (RR)=1.03; 95%CI=0.78-1.35; P=0.84]. AF ablation using CF-sensing catheters and second-generation CB showed comparable fluoroscopy duration and efficacy (during a 12-month follow-up), with shorter procedure duration and different complications in the CB group.
Assuntos
Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Criocirurgia/métodos , Ablação por Cateter/efeitos adversos , Catéteres , Ensaios Clínicos Controlados como Assunto , Criocirurgia/efeitos adversos , HumanosRESUMO
Colorectal cancer (CRC) is the fourth leading cause of cancer-induced mortality. Histone deacetylase 2 (HDAC2) is involved in prognosis and therapy of CRC. This study aimed to explore novel therapeutic targets for CRC. The alteration of HDAC2 expression in CRC tissues was estimated by qRT-PCR. After lentivirus transfection, HDAC2 knockdown was confirmed by western blot analysis. The effect of HDAC2 knockdown on cell proliferation was then assessed by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Screened by TargetScan, microRNA (miR)-455 was predicted to bind to 3'UTR of HDAC2 and the prediction was verified by luciferase assay. Finally, cells were transfected, respectively, with miR-455 mimics or miR-455 negative control (miR-NC) and the expression of HDAC2, cell proliferation and apoptosis of transfected cells were respectively evaluated by western blot analysis, MTT assay and flow cytometry. Results showed that the HDAC2 expression was up-regulated in CRC tissues (P<0.05). HDAC2 knockdown significantly decreased cell viability at day 3 (P<0.05), day 4 (P<0.01), and day 5 (P<0.001) after infection. Then, miR-455 was verified to directly target HDAC2, resulting in a significant difference in luciferase activity (P<0.01). Moreover, miR-455 decreased the expression of HDAC2 (P<0.01). miR-455 remarkably decreased cell viability at day 3 (P<0.05), day 4 (P<0.01), and day 5 (P<0.001) after transfection while inducing cell apoptosis (P<0.001). In conclusion, miR-455 inhibited cell proliferation while inducing cell apoptosis by targeting HDAC2 in CRC cells.
Assuntos
Neoplasias Colorretais/enzimologia , Histona Desacetilase 2/metabolismo , MicroRNAs/metabolismo , Idoso , Apoptose , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Neoplasias Colorretais/genética , Regulação para Baixo , Feminino , Células HCT116 , Histona Desacetilase 2/genética , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Transfecção , Regulação para CimaRESUMO
PURPOSE: To characterize the expression patterns of HDAC7 in patients with gastric cancer and evaluate the prognostic value of HDAC7 in gastric cancer. METHODS: The expression of histone deacetylase 7 (HDAC7) was detected in paraffin-embedded gastric cancer samples from 86 patients by immunohistochemistry, and the differences in the expression of HDAC7 between cancerous and corresponding adjacent noncancerous tissues were compared using the Wilcoxon matched-pairs signed rank test. The correlation between HDAC7 expression and Ki-67 expression or clinicopathologic characteristics was evaluated using a Spearman rank correlation test. Prognostic outcomes that correlated with HDAC7 were examined using a Kaplan-Meier analysis and Cox proportional hazards model. Moreover, the effects of HDAC7 on the proliferation, migration and invasion of gastric cancer cells were investigated in vitro using human gastric carcinoma AGS cells. RESULTS: We found that HDAC7 was downregulated in cancerous gastric tissues (P = 0.0019). However, the expression of HDAC7 in cancerous gastric tissues positively correlated with Ki-67 expression (P = 0.0325) and distant metastasis (P = 0.020). Moreover, overall survival was shorter for patients expressing higher levels of HDAC7 in cancerous tissues (P = 0.042). Mechanistically, the disruption of the HDAC7 gene attenuated the capacity of cell growth, migration and invasion and induced G0/G1 arrest in AGS cells. Conversely, forced ovperexpression of HDAC7 promoted cell growth, migration and invasion and G1/S transition in AGS cells. CONCLUSIONS: These results indicate that high HDAC7 expression in cancerous gastric tissues correlates with distant metastasis and predicts a poor prognosis for patients with gastric cancer.
Assuntos
Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Histona Desacetilases/metabolismo , Neoplasias Gástricas/patologia , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Ciclo Celular , Proliferação de Células , Progressão da Doença , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
Parkinson's disease (PD) is one of the most common neurodegenerative diseases and mainly manifests with decreasing numbers of dopaminergic neurons. Rapid eye movement (REM) sleep behavior disorder (RBD) has an incidence of 15-47% in all PD patients. Prion proteins (PrPs), which are expressed in both neurons and glial cells of the brain, are believed to be correlated with abnormal neurological functions, although their role in PD-related sleeping disorders remains unclear. We therefore investigated the expressional profiles of PrP in PD patients with RBD. Quantitative real-time polymerase chain reaction and western blotting were used to detect the mRNA and protein levels of PrP, respectively, in the cerebrospinal fluid (CSF) of PD patients with RBD, PD patients without sleeping disorder, and healthy people (N = 23 each). We investigated the correlation between the CSF PrP level and sleeping behavior in PD patients. Patients with PD complicated with RBD had significantly elevated CSF PrP expression levels (both mRNA and protein) compared with either PD patients without sleeping disorder or healthy individuals (P < 0.05 in both cases). There is elevated expression of PrP in the CSF of PD patients with RBD. This may benefit the diagnosis of PD-related RBD.
Assuntos
Doença de Parkinson/líquido cefalorraquidiano , Doença de Parkinson/complicações , Proteínas Priônicas/líquido cefalorraquidiano , Transtorno do Comportamento do Sono REM/líquido cefalorraquidiano , Transtorno do Comportamento do Sono REM/complicações , Expressão Gênica , Humanos , Doença de Parkinson/genética , Proteínas Priônicas/genética , Transtorno do Comportamento do Sono REM/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
PURPOSE: To investigate the potential candidate microRNA (miRNA) biomarkers for the clinical diagnosis, classification, and prognosis of gastric cancer (GC). METHODS: We use bioinformatics overlapping subclasses analysis to find the tumor grade and lymphatic metastasis-related GC specific miRNAs from the Cancer Genome Atlas (TCGA) database. Then, we further investigated these GC specific miRNAs distributions in different GC clinical features and their correlations overall survival on the basis of GC patients' information and their related RNA sequencing profile from TCGA. Finally, we randomly selected some of key miRNAs use qRT-PCR to confirm the reliability and validity. RESULTS: 22 GC specific key miRNAs were identified (Fold-change >2, P < 0.05), 11 of them were discriminatively expressed with tumor size, grade, TNM stage and lymphatic metastasis (P < 0.05). In addition, nine miRNAs (miR-196b-5p, miR-135b-5p, miR-183-5p, miR-182-5p, miR-133a-3p, miR-486-5p, miR-144-5p, miR-129-5p and miR-145-5p) were found to be significantly associated with overall survival (log-rank P < 0.05). Finally, four key miRNAs (miR-183-5p, miR-486-5p, miR-30c-2-3p and miR-133a-3p) were randomly selected to validation and their expression levels in 53 newly diagnosed GC patients by qRT-PCR. Results showed that the fold-changes between TCGA and qRT-PCR were 100 % in agreement. We also found miR-183-5p and miR-486-5p were significantly correlated with tumor TNM stage (P < 0.05), and miR-30c-2-3p and miR-133a-3p were associated with tumor differentiation degree and lymph-node metastasis (P < 0.05). These verified miRNAs clinically relevant, and the bioinformatics analysis results were almost the same. CONCLUSION: These key miRNAs may functions as potential candidate biomarkers for the clinical diagnosis, classification and prognosis for GC.
Assuntos
Adenocarcinoma/genética , Adenocarcinoma/secundário , Biomarcadores Tumorais/genética , MicroRNAs/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Idoso , Estudos de Casos e Controles , Biologia Computacional , Progressão da Doença , Feminino , Seguimentos , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Prognóstico , Taxa de SobrevidaRESUMO
OBJECTIVE: Recent studies have identified Engrailed-2 (EN-2), a homeobox-containing transcription factor, as a candidate oncogene in prostate cancer (PC). Therapeutic targeting on EN-2, however, is limited because the mechanism underlying EN-2 overexpression in prostatic cancer cells is unknown. This study was to investigate the potential regulatory role of miR-33a on EN-2 expression and explore this signaling axis in ability of prostate cancer survival and metastasis. METHODS: The relative expression of miR-33a and EN-2 in paired prostate cancer tissue and adjacent normal tissue as well as in prostate cancer cell lines, PC3 and DU145, was determined using quantitative real-time PCR or western blot, respectively. Cells survival, migration and invasion were evaluated by assays of MTT, TUNEL and Boyden chamber assays, respectively. Direct regulation of EN-2 by miR-33a was examined by luciferase reporter assay. RESULTS: The data showed that miR-33a was upregulated and EN-2 was downregulated in both prostate cancer tissue and prostate cancer cells. miR-33a overexpression suppresses prostate cancer cell survival and metastasis. miR-33a can directly act on EN-2 expression by binding to 3'UTR of its mRNA. Also, miR-33a negatively regulated EN-2 mRNA and protein expression. In pcDNA-EN-2 and miR-33a mimic co-transfected PC3 and DU145 cells, EN-2 overexpression reverses the anti-cell survival and metastasis actions of miR-33a overexpression. The pivotal role of miR-33a in inhibiting prostate tumor growth was confirmed in xenograft models of prostate cancer. CONCLUSION: Our data suggest that the functional interaction of miR-33a and EN-2 is involved in tumorigenesis of prostate cancer. Also in this process EN-2 serves as a negative responder for miR-33a.
Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Proteínas de Homeodomínio/biossíntese , MicroRNAs/genética , Proteínas do Tecido Nervoso/biossíntese , Neoplasias da Próstata/patologia , Animais , Apoptose/genética , Western Blotting , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo , Xenoenxertos , Proteínas de Homeodomínio/genética , Humanos , Marcação In Situ das Extremidades Cortadas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Proteínas do Tecido Nervoso/genética , Neoplasias da Próstata/genética , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Colorectal cancer (CRC) is the fourth leading cause of cancer-induced mortality. Histone deacetylase 2 (HDAC2) is involved in prognosis and therapy of CRC. This study aimed to explore novel therapeutic targets for CRC. The alteration of HDAC2 expression in CRC tissues was estimated by qRT-PCR. After lentivirus transfection, HDAC2 knockdown was confirmed by western blot analysis. The effect of HDAC2 knockdown on cell proliferation was then assessed by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Screened by TargetScan, microRNA (miR)-455 was predicted to bind to 3′UTR of HDAC2 and the prediction was verified by luciferase assay. Finally, cells were transfected, respectively, with miR-455 mimics or miR-455 negative control (miR-NC) and the expression of HDAC2, cell proliferation and apoptosis of transfected cells were respectively evaluated by western blot analysis, MTT assay and flow cytometry. Results showed that the HDAC2 expression was up-regulated in CRC tissues (P<0.05). HDAC2 knockdown significantly decreased cell viability at day 3 (P<0.05), day 4 (P<0.01), and day 5 (P<0.001) after infection. Then, miR-455 was verified to directly target HDAC2, resulting in a significant difference in luciferase activity (P<0.01). Moreover, miR-455 decreased the expression of HDAC2 (P<0.01). miR-455 remarkably decreased cell viability at day 3 (P<0.05), day 4 (P<0.01), and day 5 (P<0.001) after transfection while inducing cell apoptosis (P<0.001). In conclusion, miR-455 inhibited cell proliferation while inducing cell apoptosis by targeting HDAC2 in CRC cells.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Neoplasias Colorretais/enzimologia , Histona Desacetilase 2/metabolismo , MicroRNAs/metabolismo , Apoptose , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Neoplasias Colorretais/genética , Regulação para Baixo , Células HCT116 , Histona Desacetilase 2/genética , MicroRNAs/genética , Transfecção , Regulação para CimaRESUMO
This meta-analysis compared the efficacy and safety of the contact force (CF)-sensing catheter and second-generation cryoballoon (CB) ablation for treating atrial fibrillation (AF). Six controlled clinical trials comparing ablation for AF using a CF-sensing catheter or second-generation CB were identified from PubMed, EMBASE, Cochrane Library, Wanfang Data, and China National Knowledge Infrastructure. The procedure duration was significantly lower in the CB group compared with that in the CF group [mean difference (MD)=29.4; 95%CI=17.84-40.96; P=0.01], whereas there was no difference between the groups for fluoroscopy duration (MD=0.59; 95%CI=-4.48-5.66; P=0.82). Moreover, there was no difference in the incidence of non-lethal complications (embolic event, tamponade, femoral/subclavian hematoma, arteriovenous fistula, pulmonary vein stenosis, phrenic nerve palsy, and esophageal injury) between the CB and the CF groups (8.38 vs 5.35%; RR=0.66; 95%CI=0.37-1.17; P=0.15). Transient phrenic nerve palsy occurred in 17 of 326 patients (5.2%) of the CB group vs none in the CF group (RR=0.12; 95%CI=0.03-0.43; P=0.001). A comparable proportion of patients in CF and CB groups suffered from AF recurrence during the 12-month follow-up after a single ablation procedure [risk ratio (RR)=1.03; 95%CI=0.78-1.35; P=0.84]. AF ablation using CF-sensing catheters and second-generation CB showed comparable fluoroscopy duration and efficacy (during a 12-month follow-up), with shorter procedure duration and different complications in the CB group.
Assuntos
Humanos , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Criocirurgia/métodos , Ablação por Cateter/efeitos adversos , Ensaios Clínicos Controlados como Assunto , Criocirurgia/efeitos adversos , CatéteresRESUMO
Glucosinolates (GSLs) are important secondary metabolites in Brassicaceae plants. Previous studies have mainly focused on GSL contents, types, and biosynthesis-related genes, but the molecular characterization patterns of GSL biosynthesis-related transcription factors remain largely unexplored in radish (Raphanus sativus L.). To isolate transcription factor genes regulating the GSL biosynthesis, genomic DNA and cDNA sequences of RsMYB28 and RsMYB29 genes were isolated in radish. Two R2R3-MYB domains were identified in the deduced amino acid sequences. Subcellular localization and yeast-one hybrid assays indicated that both the RsMYB28 and RsMYB29 genes were located in the nucleus and possessed transactivation activity. Reverse transcription quantitative analysis showed that the RsMYB28 and RsMYB29 genes were expressed in seeds, leaves, stems, and roots at the seedling, taproot thickening, and mature stages. Both genes were highly expressed during the seedling and taproot thickening stages. The expression level of RsMYB28 was found to be up-regulated following wounding, glucose, and abscisic acid treatments, whereas RsMYB29 was up-regulated following wounding and methyl jasmonate treatments. These results provide insights into the biological function and characterization of the RsMYB28 and RsMYB29 genes, and facilitate further dissection of the molecular regulatory mechanism underlying the GSL biosynthesis in radish.
Assuntos
Genes de Plantas , Proteínas de Plantas/genética , Raphanus/genética , Fatores de Transcrição/genética , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Glucosinolatos/metabolismo , Cebolas/citologia , Peptídeos/química , Filogenia , Epiderme Vegetal/citologia , Proteínas de Plantas/metabolismo , Frações Subcelulares/metabolismo , Fatores de Transcrição/metabolismo , Ativação Transcricional/genéticaRESUMO
The mammalian hair follicle (HF) is a unique, highly regenerative organ with a distinct developmental cycle. Cashmere goat (Capra hircus) HFs can be divided into two categories based on structure and development time: primary and secondary follicles. To identify differentially expressed genes (DEGs) in the primary and secondary HFs of cashmere goats, the RNA sequencing of six individuals from Arbas, Inner Mongolia, was performed. A total of 617 DEGs were identified; 297 were upregulated while 320 were downregulated. Gene ontology analysis revealed that the main functions of the upregulated genes were electron transport, respiratory electron transport, mitochondrial electron transport, and gene expression. The downregulated genes were mainly involved in cell autophagy, protein complexes, neutrophil aggregation, and bacterial fungal defense reactions. According to the Kyoto Encyclopedia of Genes and Genomes database, these genes are mainly involved in the metabolism of cysteine and methionine, RNA polymerization, and the MAPK signaling pathway, and were enriched in primary follicles. A microRNA-target network revealed that secondary follicles are involved in several important biological processes, such as the synthesis of keratin-associated proteins and enzymes involved in amino acid biosynthesis. In summary, these findings will increase our understanding of the complex molecular mechanisms of HF development and cycling, and provide a basis for the further study of the genes and functions of HF development.