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Up to date, the mechanism of gastric cancer (GC) development is poorly understood. This study was to demonstrate the effects of LINC00339 on GC progression. Here, we found that LINC00339 was overexpressed expressed in GC tissues and predicted poor outcome. By CCK8, colony formation and Transwell assays, we showed LINC00339 knockdown suppressed GC cell proliferation, migration, and invasion in vitro. Flow cytometry analysis (FACS) indicated that LINC00339 knockdown induced tumor cell apoptosis. Besides, we utilized the xenograft assay and found that LINC00339 depletion led to decreased tumor growth in vivo. Mechanistically, miR-377-3p was found to be inhibited by LINC00339. And LINC00339 suppressed miR-377-3p to upregulate DCP1A, which consequently promoted GC progression. In conclusion, LINC00339 promotes gastric cancer progression by elevating DCP1A expression via inhibiting miR-377-3p.
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Endorribonucleasas/biosíntesis , MicroARNs/genética , ARN Largo no Codificante/genética , Neoplasias Gástricas/patología , Transactivadores/biosíntesis , Apoptosis/genética , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Humanos , Invasividad Neoplásica/genética , Trasplante de Neoplasias , Oncogenes/genética , Interferencia de ARN , ARN Interferente Pequeño/genética , Neoplasias Gástricas/genética , Trasplante HeterólogoRESUMEN
Increasing data demonstrate that circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs) play important roles in tumorigenesis. However, the mechanisms in colorectal cancer (CRC) remain unclear. Here, hundreds of significantly expressed circRNAs, and thousands of lncRNAs as well as mRNAs were identified. By qRT-PCR, one abnormal circRNA, lncRNA, and three mRNAs were verified in 24 pairs of tissues and blood samples, respectively. Then, by GO analysis, we found that the gene expression profile of linear counterparts of upregulated circRNAs in human CRC tissues preferred positive regulation of GTPase activity, cellular protein metabolic process, and protein binding, while that of downregulated circRNAs of CRC preferred positive regulation of cellular metabolic process, acetyl-CoA metabolic process, and protein kinase C activity. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that p53 signaling pathway was an important pathway in upregulated protein-coding genes, whereas cyclic guanosine monophosphate-protein kinase G (cGMP-PKG) signaling pathway was the top enriched KEGG pathway for downregulated transcripts. Furthermore, lncRNA-mRNA co-expression analysis demonstrated that downregulated lncRNA uc001tma.3 was negatively with CDC45 and positively with ELOVL4, BVES, FLNA, and HSPB8, while upregulated lncRNA NR_110882 was positively with FZD2. In addition, lncRNA-transcription factor (TF) co-expression analysis showed that the most relevant TFs were forkhead box protein A1 (FOXA1), transcription initiation factor TFIID submint 7 (TAF7), and adenovirus early region 1A(E1A)-associated protein p300 (EP300). Our findings offer a fresh view on circRNAs and lncRNAs and provide the foundation for further study on the potential roles of circRNAs and lncRNAs in colorectal cancer.
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Ácidos Nucleicos Libres de Células/genética , Neoplasias Colorrectales/genética , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , ARN Largo no Codificante/genética , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Ácidos Nucleicos Libres de Células/sangre , Neoplasias Colorrectales/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Largo no Codificante/sangreRESUMEN
A meta-analysis was performed to examine the efficiency and safety of trastuzumab in patients with advanced gastric and gastroesophageal cancer (AGC). By searching multiple databases from 1990 to March 2016, all randomized controlled trials (RCTs) which compared the effect of trastuzumab-combined chemotherapy (TC) versus chemotherapy alone (CT) in gastric cancer would be included. Five RCTs with a total of 875 patients were included. Trastuzumab can improve the overall survival (OS) rate, progression-free survival (PFS), one-year survival rate, two-year survival rate and overall response rate (ORR) of patients with AGC. There were no difference between the two arms in terms of grade 3/4 adverse effects, such as vomiting, nausea, neutropenia, thrombocytopaenia and anemia. Diarrhea increased in TC group. Trastuzumab can significantly improve the survival rate, PFS, ORR of patients with AGC. It is safe and feasible and can be tolerated. It needs further prospective multinational multicenter RCTs with large samples to define the clinical benefits of trastuzumab.
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Antineoplásicos/efectos adversos , Carcinoma/tratamiento farmacológico , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Trastuzumab/efectos adversos , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de Supervivencia , Trastuzumab/administración & dosificación , Trastuzumab/uso terapéuticoRESUMEN
NHHR (non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio) is a novel lipid parameter. However, the association between NHHR and sleep disorders remains unknown.; A cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2005 to 2016. The association between NHHR and sleep disorders was explored using weighted multivariate logistic regression and generalized summation models. Subgroup analyses were employed to verify the robustness of this association. The prevalence of sleep disorders was 25.83% in a total of 22,221 participants. Compared to the lowest quartile of NHHR, participants in the top quartile had a 14% higher odds of sleep disorders prevalence in fully adjusted model (OR: 1.14, 95% CI: 1.06-1.23). After subgroup analyses and interaction tests, sex, race, marital status, education level, body mass index (BMI), person income ratio (PIR), alcohol consumption, smoking status, hypertension, and diabetes mellitus were not significantly associated with this positive association (P for interactionâ >â 0.05). The NHHR is positively associated with sleep disorders in US adults. The management and monitoring of NHHR may have a potential role in improving sleep disorders.
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HDL-Colesterol , Encuestas Nutricionales , Trastornos del Sueño-Vigilia , Humanos , Masculino , Femenino , Estados Unidos/epidemiología , Estudios Transversales , Trastornos del Sueño-Vigilia/epidemiología , Trastornos del Sueño-Vigilia/sangre , Persona de Mediana Edad , Adulto , HDL-Colesterol/sangre , Prevalencia , Factores de Riesgo , AncianoRESUMEN
Following the publication of the above article, a concerned reader drew to the Editor's attention that the data showing the results of TUNEL staining of tumours featured in the four panels of Fig. 2G on p. 4, and potentially some of the photographs of the tumours shown in Fig. 2F, were strikingly similar to data appearing in different form in another article written by different authors that had already been submitted for publication elsewhere prior to the submission of this paper to Oncology Reports. In view of the fact that certain of these data had already apparently been submitted for submission in a different journal, the Editor of Oncology Reports has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they accepted the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Oncology Reports 46: 142, 2021; DOI: 10.3892/or.2021.8093].
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BACKGROUND: Small bowel cancer (SBC) is a very rare solid malignancy. Consequently, compared with other malignant gastrointestinal tumors, our knowledge regarding SBC, specifically its molecular attributes, remains limited. Herein, we aim to provide an overview of the gene characteristics of Chinese patients with SBC, We particularly focus on elucidating the genetic intricacies that differentiate SBC patients whose primary tumors originate in distinct anatomical regions within the small bowel. METHODS: During the period ranging from February 2018 to December 2022, a total of 298 tumor samples were consecutively collected from Chinese patients diagnosed with small bowel cancer.. Next-generation sequencing (NGS) was performed to detect gene mutation, assess microsatellite instability (MSI), and evaluate tumor mutational burden (TMB). Additionally,, IHC was used to analyze the level of PD-L1 expression within the samples. RESULTS: The outcomes of the next-generation sequencing (NGS) unveiled the predominant gene mutations observed in Chinese patients with small bowel cancer (SBC). The top ten gene mutations identified were as follows: TP53 (53%), KRAS (51%), APC (31%), SMAD4 (19%), VEGFA (15%), CDKN2A (15%), RAC1 (15%), LRP1B (14%), MGMT (14%, CD74 (13%). Subsequent analysis revealed disparities in the gene landscape between the cohort in this study and that of the Memorial Sloan Kettering Cancer Center (MSKCC), Notably, distinguishable mutational frequencies were identified in several genes, including ERBB2, FBXW7, PIK3CA, etc. which exhibited contrasting presence in both this cohort and the MSKCC cohort.. Furthermore, we noticed variations in the frequency of gene mutations among SBC patients depending on the specific anatomical site where the tumors originated within the small bowel. In addition, the distribution of patients with high microsatellite instability (MSI-H) and tumor mutational burden (TMB) levels varied among SBC patients with tumors originating from the duodenum, jejunum, and ileum. CONCLUSION: Chinese patients with small bowel cancer exhibited a distinct genetic profile in comparison to other populations, highlighting a unique genetic landscape. Furthermore, noticeable disparities in the genetic landscape were observed between patients with cancer situated in the duodenum and those with cancer affecting other regions of the small bowel, this suggests that these patients should be treated differently.
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Neoplasias Colorrectales , Inestabilidad de Microsatélites , Humanos , Pueblos del Este de Asia , Perfil Genético , Mutación , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/genéticaRESUMEN
Background: The number of lymph nodes examined (LNe) is often insufficient in patients with rectal cancer (RC) treated with neoadjuvant therapy; however, its prognostic value remains controversial. Thus, we retrospectively explored whether LNe had an influence on staging and prognosis and investigated whether there was a cut-off value for better prognosis in patients with RC treated with neoadjuvant therapy. Methods: Data were collected from seven prospective hospital databases in China from July 2002 to May 2018. Binary logistic regression models were used to predict lymph node metastasis. The cut-off value for LNe was determined using X-tile 3.6.1. Survival outcomes and risk factors were analyzed using the log-rank test and Cox regression model. Results: A total of 482 patients were included, of whom 459 had complete overall survival (OS) information. Using the percentile method, the total number of lymph nodes examined (TLNe) was 14-16 (40th-60th percentile), and the proportion of patients with lymph node metastasis reached a maximum of 48.1%. Cox multivariate analysis showed that the odds ratio (OR) remained the highest when TLNe was 14-16 (OR = 3.379, P = 0.003). The 3-year and 5-year OS were 85.4% and 77.8%, respectively. Negative lymph nodes examined (NLNe) of ≤6 was an independent risk factor for 3-year and 5-year OS (3-year OS 71.1% vs. 85.9%, P = 0.004; 5-year OS 66.3% vs. 74.3%, P = 0.035). Subgroup analysis for patients with ypN + showed that higher 3-year and 5-year OS were achieved when the TLNe was >10, 78.8% vs. 54.0% (P = 0.005), and 60.8% vs. 36.0% (P = 0.012), respectively. Patients with ypN0M0 had a higher 5-year OS when the TLNe was >19 (P = 0.055). Conclusion: The TLNe and NLNe influenced the staging accuracy and demonstrated prognostic value in patients with RC treated with neoadjuvant therapy.
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Aberrant expression of circular RNAs (circRNAs) has been demonstrated to be related to the development of colorectal cancer (CRC), the third most common cancer worldwide. However, the mechanism of the effect of circRNA NOP2/Sun domain family, member 2 (circNSUN2) on the malignant biological behavior of CRC remains unclear. In the present study, the expression of circNSUN2 and microRNA (miR)181a5p was detected by RTqPCR. The expression of Rhoassociated coiledcoilcontaining protein kinase 2 (ROCK2) was measured by western blotting. Cell proliferation was detected by CCK8 assay. The cell apoptosis rate was measured by flow cytometry. Cell migration ability was evaluated by Transwell assay. The interactions between circNSUN2, miR181a5p and ROCK2 were verified by dualluciferase reporter assay. The results revealed that circNSUN2 was highly expressed in CRC tissues and cell lines. Knockdown of circNSUN2 inhibited the malignant biological behavior of CRC in vivo and in vitro. Moreover, miR181a5p was revealed to be a target gene of circNSUN2, and the expression of ROCK2 was negatively regulated by miR181a5p. Knockdown of circNSUN2 inhibited proliferation and migration, and induced apoptosis of CRC cells and suppressed tumor growth by targeting miR181a5p to decrease ROCK2 expression. In conclusion, circNSUN2 promoted the progression of CRC by sponging miR181a5p to increase the expression of ROCK2.
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Neoplasias Colorrectales/patología , MicroARNs/genética , ARN Circular/genética , Quinasas Asociadas a rho/genética , Quinasas Asociadas a rho/metabolismo , Adulto , Animales , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Células HCT116 , Humanos , Masculino , Ratones , Persona de Mediana Edad , Trasplante de Neoplasias , Regulación hacia Arriba , Adulto JovenRESUMEN
Mucin1 (MUC1) upregulation in colon cancer has been linked to poor patient outcomes and advanced stage at diagnosis. This is partially due to MUC1-mediated inhibition of T-cell proliferation affecting efficient lysis by cytotoxic lymphocytes, which contributes to escape from immune surveillance. In the present study, human colorectal cancer tissues were collected, and MUC1-positive and MUC1-negative colon cancer mouse models were prepared; subsequently, the number and function of immune cells in tumor tissues were measured using flow cytometry. The present study revealed that MUC1, as a tumor-associated antigen, can recruit more tumor-infiltrating lymphocytes into the tumor microenvironment compared with MUC1-negative colon cancer, but that these cells could not serve antitumor roles. Conversely, the present study demonstrated that MUC1-positive colon cancer attracted more regulatory T cells (Treg cells), myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) to the tumor site than MUC1-negative colon cancer. Furthermore, the data suggested that programmed death protein 1 (PD1)-programmed death ligand 1 (PDL1) expression is greater in MUC1-positive colon cancer. Blocking the PD1-PDL1 signaling pathway reduced the percentage of Treg cells, MDSCs and TAMs in the tumor microenvironment, enhanced T-cell cytotoxicity and inhibited tumor growth, prolonging the survival time of MUC1-positive tumor-bearing mice. Therefore, the present study elucidated the role of MUC1 in tumor immune escape and provides a foundation for the application of PDL1 inhibitors to MUC1-positive colon cancer.
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PURPOSE: The aim of this study was to research the function of lncRNA LUCAT1 in gastric cancer. METHODS: Human gastric cancer tissues and paracancer tissues were obtained from 98 patients undergoing surgical resection in our hospital. The human gastric cancer cell lines (HGC27, BGC823, MGC803, SGC7901 and AGS), and normal gastric mucosal cell line GSE1 were used to research the role of lncRNA LUCAT1. ShRNAs specifically targeting lncRNA LUCAT1, miR-134-5p mimic, miR-134-5p inhibitor and their related controls were transfected into cells. Quantitative real-time PCR was used to detect the expression of lncRNA LUCAT1, miR-134-5p and YWHAZ. The cell proliferation of SGC7901 cells was determined by CCK8 kit. Colony formation assay was undertaken. Cell apoptosis assay was processed using the Annexin V-FITC / propidium iodide (annxinV/PI) apoptosis detection kit. Migration and invasion were detected by transwell assay. Tumor xenograft model was conducted to calculate the size and weight of the tumors. Luciferase reporter assay was used to confirm the interactions among lncRNA LUCAT1, miR-134-5p and YWHAZ. RESULTS: LncRNA LUCAT1 was confirmed to be highly expressed in gastric cancer. Patients with high LUCAT1 level displayed short overall survival and disease-free survival periods. LUCAT1 knockdown or miR-134-5p overexpression decreased the proliferation, colony formation, migration and invasion of SGC7901 cells. CONCLUSIONS: LncRNA LUCAT1 could promote proliferation and invasion of gastric cancer by regulating miR-134-5p/YWHAZ axis.
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Proteínas 14-3-3/metabolismo , Movimiento Celular/genética , Proliferación Celular/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , Neoplasias Gástricas/patología , Proteínas 14-3-3/genética , Anciano , Apoptosis/genética , Línea Celular Tumoral , Femenino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patología , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , MicroARNs/genética , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasias Gástricas/genéticaRESUMEN
The aberrant expression of ceroid-lipofuscinosis 3 (CLN3) has been reported in a variety of human malignancies. However, the role of CLN3 in the progression and prognosis of hepatocellular carcinoma (HCC) remains unknown. In this study, we found that CLN3 was frequently upregulated in HCC clinical samples and HCC-derived cell lines and was significantly correlated with an APF serum level ≥20⯵g/L, a tumour size ≥5â¯cm, multiple tumours, and the absence of encapsulation. Kaplan-Meier showed that CLN3 upregulation predicted shorter recurrence-free survival (RFS) and overall survival (OS) time in HCC patients. Cox regression analysis revealed that CLN3 upregulation was an independent risk factor for RFS and OS. A functional study demonstrated that the knockdown of CLN3 expression profoundly suppressed the growth and metastasis of HCC cells both in vitro and in vivo. Mechanistic investigation revealed that the EGFR/PI3K/AKT pathway was essential for mediating CLN3 function. In conclusion, our results provide the first evidence that CLN3 contributes to tumour progression and metastasis and offer a potential prognostic predictor and therapeutic target for HCC.
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Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Glicoproteínas de Membrana/metabolismo , Chaperonas Moleculares/metabolismo , Recurrencia Local de Neoplasia/patología , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Movimiento Celular , Proliferación Celular , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Glicoproteínas de Membrana/genética , Persona de Mediana Edad , Chaperonas Moleculares/genética , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/metabolismo , Pronóstico , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVES: To investigate the expression of caspase-8 and -10 in rectal adenoma, adenocarcinoma and the corresponding normal mucosa tissue, and to clarify the relationship between their expression and clinicopathological parameters of rectal cancer. METHODS: The expression of caspase-8 and -10 was determined by real-time RT-PCR and immunohistochemistry in 36 rectal adenomas, 93 rectal cancers and 93 corresponding normal rectal mucosa samples. RESULTS: Compared with normal mucosa, the mRNA expression of caspase-8 was higher in adenomas (p = 0.003), while that of caspase-10 was lower in adenomas (p = 0.035) and cancers (p = 0.001). Immunohistochemical results showed caspase-8 up-regulation in adenomas (p = 0.014), and caspase-10 down-regulation in adenomas (p = 0.034) and cancers (p < 0.001) compared with normal mucosa samples. Cancers with poor differentiation had lower caspase-10 mRNA and protein levels than those with better differentiation (p = 0.041 and p = 0.046, respectively). The protein expression of caspase-8 and -10 was in accordance with the mRNA expression (p = 0.043 and p = 0.018, respectively). CONCLUSIONS: Caspase-8 expression was up-regulated in rectal adenomas. Caspase-10 expression was down-regulated in both rectal adenomas and cancers, and was further related to differentiation. Caspase-8 and -10 may be involved in the pathogenesis of rectal cancer.
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Adenoma/metabolismo , Caspasa 10/metabolismo , Caspasa 8/metabolismo , Neoplasias del Recto/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/metabolismo , Adenocarcinoma Mucinoso/patología , Adenoma/genética , Adenoma/patología , Carcinoma de Células en Anillo de Sello/genética , Carcinoma de Células en Anillo de Sello/metabolismo , Carcinoma de Células en Anillo de Sello/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Caspasa 10/genética , Caspasa 8/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Membrana Mucosa/metabolismo , Membrana Mucosa/patología , Invasividad Neoplásica , Estadificación de Neoplasias , Pronóstico , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Neoplasias del Recto/genética , Neoplasias del Recto/patología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: In patients suffering from acute pancreatitis, the pathogenesis is not completely understood, and several recent studies in vitro suggested that heat shock proteins might play an important role in cell signaling. To investigate the possible role of extracellular heat shock protein 70 (Hsp70) in pancreatitis, toll-like receptor-4 (TLR4)-deficient and wild-type mice were administered with exogenous Hsp70 during the course of cerulein-induced pancreatitis (CIP). METHODS: Acute pancreatitis was induced by 5 intraperitoneal injections of cerulein at hourly intervals, and then treated with recombinant Hsp70 through the caudal vein 4 hours after the start of cerulein injections. Subsequently serum amylase and serum cytokines levels were detected. Histologic alteration of the pancreas was evaluated. Tumor necrosis factor alpha (TNF-alpha) concentrations and myeloperoxidase (MPO) activity in both pancreas and lungs were analyzed. The nuclear factor kappa B (NF-kappaB) activation in pancreatic tissue was measured using a sensitive RelA enzyme-linked immunosorbent assay. RESULTS: Treatment with recombinant Hsp70 to wild-type mice in CIP resulted in significant aggravation of inflammation in pancreas, elevated levels of serum cytokines, up-regulation of pulmonary MPO activity and increase of lung tissues TNF-alpha concentrations. In contrast, treatment with Hsp70 to TLR4-deficient mice had little effect on serum cytokines levels, pancreatic inflammation, pulmonary MPO activity and TNF-alpha concentrations. CONCLUSIONS: The results suggest that extracellular Hsp70 might induce systemic inflammatory response syndrome (SIRS)-like response in vivo and TLR4 might be involved in the Hsp70-mediated activation of inflammatory reaction in the progression of CIP without infection.
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Ceruletida/toxicidad , Proteínas HSP70 de Choque Térmico/fisiología , Pancreatitis/etiología , Receptor Toll-Like 4/fisiología , Enfermedad Aguda , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Síndrome de Respuesta Inflamatoria Sistémica/etiologíaRESUMEN
The aim of the present study was to investigate the effects of Tolllike receptor (TLR) 9 and CpG oligodeoxynucleotide (CpGODN)1826 on sodium taurocholateinduced acute pancreatitis (AP) rats at different time points. Pathological examination indicated that the severity of pancreatic tissue damage following AP increased with time. Additionally, TLR9 protein levels were upregulated after AP, and were higher at 6 h compared with at 3 h. Subsequently, the TLR9 protein levels were downregulated at 12 h, but remained higher than the control group. In rats subjected to AP, tumor necrosis factor (TNFα protein expression levels and serum amylase (AMS) in the serum were increased until 12 h. The expression level of TNFα protein in the AP 12 h group was higher than that in the AP 3 and 6 h groups. In addition, following CpGODN1826 administration, the morphology of pancreatic tissue appeared worse compared with that in the AP only groups. Furthermore, CpGODN1826 administration induced an increase in TLR9 expression levels compared with the AP alone group at 0, 3, 6 and 12 h. TNFα in the CpG + AP 12 h group was upregulated compared with that in the CpG + AP 3 and 6 h groups; however, no change was observed between 3 and 6 h. Thus, these data indicate that CpGODN1826 aggravates sodium taurocholateinduced pancreas damage in rats.
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Oligodesoxirribonucleótidos/inmunología , Páncreas/inmunología , Pancreatitis/inmunología , Receptor Toll-Like 9/inmunología , Enfermedad Aguda , Animales , Modelos Animales de Enfermedad , Masculino , Páncreas/patología , Pancreatitis/inducido químicamente , Pancreatitis/patología , Ratas , Ratas Sprague-Dawley , Ácido Taurocólico , Receptor Toll-Like 9/análisisRESUMEN
Lungs are the most common extraabdominal site of metastasis of colorectal cancer (CRC), in which long noncoding RNA (lncRNA) may serve a role. In the present study, a highthroughput microarray assay was performed to detect lncRNA expression and identify novel targets for further study of lung metastasis in CRC. In the CRC tissues from patients with lung metastasis, 7,632 lncRNA (3,574 upregulated and 4,058 downregulated) and 6,185 mRNA (3,394 upregulated and 2,791 downregulated) were detected to be differentially expressed with a fold change ≥2 and P<0.05 compared with the CRC tissues without metastasis. A total of six differentially regulated lncRNA were confirmed by reverse transcriptionquantitative polymerase chain reaction in 20 pairs of CRC samples. Furthermore, gene ontology and pathway analysis were conducted to predict the possible roles of the identified mRNA. The upregulated mRNA were associated with cell division (biological processes), protein kinase B binding (molecular functions) and cellular components. The downregulated mRNA were associated with cell adhesion, plateletderived growth factor binding and membrane components. Pathway analysis determined that the upregulated mRNA were associated with the Wnt signaling pathway in the CRC tissues from patients with lung metastasis, while the downregulated mRNA were associated with the phosphoinositide 3kinase/Akt signaling pathway. The results of the present study suggested that differentially expressed lncRNA may be associated with lung metastasis and may provide insights into the biology and prevention of lung metastasis.
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Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Pulmonares/secundario , ARN Largo no Codificante/genética , ARN Mensajero/genética , Anciano , División Celular/genética , Biología Computacional/métodos , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Ontología de Genes , Humanos , Masculino , Persona de Mediana Edad , Anotación de Secuencia Molecular , Estabilidad del ARN , Reproducibilidad de los ResultadosRESUMEN
PURPOSE: This study aimed to probe into the associations among circular RNA ZFR (circ-ZFR), miR-130a/miR-107, and PTEN, and to investigate the regulatory mechanism of circ-ZFRâmiR-130a/miR-107âPTEN axis in gastric cancer (GC). MATERIALS AND METHODS: GSE89143 microarray data used in the study were acquired from publicly available Gene Expression Omnibus database to identify differentially expressed circular RNAs inGC tissues. The expressions of circ-ZFR, miR-130a, miR-107, and PTEN were examined by real-time reverse transcription polymerase chain reaction, while PTEN protein expression was measured by western blot. The variation of GC cell proliferation and apoptosis was confirmed by cell counting kit-8 assay and flow cytometry analysis. The targeted relationships among circZFR, miR-130a/miR-107, and PTEN were predicted via bioinformatics analysis and demonstrated by dual-luciferase reporter assay and RNA immunoprecipitation assay. The impact of ZFR on gastric tumor was further verified in xenograft mice model experiment. RESULTS: Circ-ZFR and PTEN were low-expressed whereas miR-107 and miR-130a were highexpressed in GC tissues and cells. There existed targeted relationships and interactions between miR-130a/miR-107 and ZFR/PTEN. Circ-ZFR inhibited GC cell propagation, cell cycle and promoted apoptosis by sponging miR-107/miR-130a, while miR-107/miR-130a promoted GC cell propagation and impeded apoptosis through targeting PTEN. Circ-ZFR inhibited cell proliferation and facilitated apoptosis in GC by sponging miR-130a/miR-107 and modulating PTEN. Circ-ZFR curbed GC tumor growth and affected p53 protein expression in vivo. CONCLUSION: Circ-ZFR restrained GC cell proliferation, induced cell cycle arrest and promoted apoptosis by sponging miR-130a/miR-107 and regulating PTEN.
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MicroARNs/genética , Fosfohidrolasa PTEN/genética , ARN/genética , Neoplasias Gástricas/patología , Animales , Apoptosis , Línea Celular Tumoral , Proliferación Celular , Bases de Datos de Ácidos Nucleicos , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Trasplante de Neoplasias/patología , Análisis de Secuencia por Matrices de Oligonucleótidos , Fosfohidrolasa PTEN/metabolismo , ARN Circular , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismoRESUMEN
OBJECTIVE: To examine E1AF mRNA expression and to determine whether it is correlated with tumor progression and matrilysin in human rectal cancer. METHODS: Real-time RT-PCR was used to determine E1AF and matrilysin expression in 100 matched rectal cancers and normal tissues. RESULTS: Among the 100 rectal cancers, 69 cases of E1AF mRNA overexpression were observed. E1AF mRNA overexpression correlated well with matrilysin. In carcinomas, E1AF mRNA overexpression correlated significantly with depth of invasion, lymph node metastasis, venous involvement and advanced pTNM stage. CONCLUSIONS: E1AF was correlated significantly with tumor progression of human rectal cancer and may be an important factor in rectal cancer progression.
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Proteínas E1A de Adenovirus/genética , Metaloproteinasa 7 de la Matriz/genética , Proteínas Proto-Oncogénicas/genética , ARN Mensajero/genética , Neoplasias del Recto/genética , Anciano , Progresión de la Enfermedad , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Proteínas Proto-Oncogénicas c-ets , ARN Neoplásico/genética , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Recto/patología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
The lung is the most common extra-abdominal site of metastasis in colorectal cancer (CRC), in which circular RNA (circRNA) may have a crucial role. Therefore, the present study detected circRNA expression to identify novel targets to further study lung metastasis in CRC. In the present study, total RNA was extracted from CRC tissues of patients with and without lung metastasis to perform high-throughput microarray assay in order to detect differentially expressed circRNA. Following this, gene ontology (GO) and pathway analyses of the genes producing differentially expressed circRNA were performed to predict the function of circRNA using standard enrichment computational methods. Additionally, the circRNA/microRNA (miRNA) interactions were constructed with bioinformatics methods to predict the binding of miRNA with circRNA. In the CRC tissues from patients with lung metastasis, 431 circRNA were detected to be differentially expressed, including 192 upregulated and 239 downregulated over 2-fold compared with the CRC tissues without metastasis. Furthermore, GO analysis revealed that the genes producing upregulated circRNA were involved in DNA repair, while the genes producing downregulated circRNA were enriched in signal transduction. By pathway analysis, it was identified that the genes producing downregulated circRNA were involved in the nuclear factor-κB and Wnt signaling pathway in the CRC tissues from patients with lung metastasis compared with the CRC tissues without metastasis. In addition, it was demonstrated that hsa_circRNA_105055, hsa_circRNA_086376 and hsa_circRNA_102761 could commonly bind with miR-7 regulating target genes PRKCB, EPHA3, BRCA1 and ABCC1. The findings of the present study may provide a novel perspective on circRNA and lay a foundation for future research of potential roles of circRNA in CRC with lung metastasis.
Asunto(s)
Neoplasias Colorrectales/genética , Neoplasias Pulmonares/genética , MicroARNs/genética , ARN/genética , Anciano , Neoplasias Colorrectales/patología , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/genética , Ontología de Genes , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN CircularRESUMEN
Human immunodeficiency virus1 (HIV1) infection severely damages the gutassociated lymphoid tissue (GALT), the immune system and the gut barrier, which leads to accelerating the disease progression for patients with acquired immune deficiency syndrome (AIDS). Dysregulation of microRNAs (miRNAs) may contribute to this process. However, few studies have investigated the importance of miRNAs in AIDS pathogenesis and progression. The whole miRNA profile of patients with HIV infection from southwest P.R. China and the mode of interaction between HIV1 and miRNAs remains to be elucidated. Colon mucosal samples were collected from HIV+ patients and HIV healthy individuals, miRNAs were isolated and subjected to array hybridization in the present study. A total of 476 human and virusderived microRNAs were significantly altered in the HIV+ group when compared with the control group (P<0.05), which may be involved in the progression to AIDS. Target genes of the significantly altered miRNAs were predicted using the TargetScan, miRbase and miRanda databases and the 10 shared target genes of upregulated miRNAs and the 391 target genes of downregulated miRNAs were selected. As only 10 target genes were predicted for upregulated miRNAs, subsequent GO and KEGG pathway analyses were focused on the 391 target genes of the downregulated miRNAs. The findings of the present study identified a series of crucial pathways, including cellextracellular matrix interaction and chemokine regulation, which indicated close affinity with CD4+ T cell activation. These pathways, involving genes such as integrin α5, led to a gut barrier dysfunction of patients with HIV. Important miRNAs include hsamiRNA325p, hsamiRNA1955p, hsamiRNA20b5p, hsamiRNA5905p. The expression levels of the miRNAs and their target genes were confirmed using RTqPCR. Taking into previous observations, the findings of the present study identified the importance of miRNAs for regulating gut barrier dysfunction via multiple regulatory molecules and signaling pathways, which elucidated the underlying molecular mechanism of gut barrier dysfunction in patients with HIV.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/genética , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Interacciones Huésped-Patógeno/genética , Mucosa Intestinal/metabolismo , MicroARNs/genética , Transcriptoma , Síndrome de Inmunodeficiencia Adquirida/inmunología , Síndrome de Inmunodeficiencia Adquirida/patología , Síndrome de Inmunodeficiencia Adquirida/virología , Adulto , Recuento de Linfocito CD4 , Estudios de Casos y Controles , Biología Computacional/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Carga ViralRESUMEN
Falconiformes include most of the predatory birds, they play crucial role in maintaining the balance of ecology system. To further illustrate the phylogenetic status for the species of Falconiformes, the entire mitochondrial DNA (mtDNA) genome of Falco naumanni was amplified and sequenced, further phylogenetic analysis was performed by incorporating with other 8 entire mtDNA genomes representing 8 species of predatory birds by taking the Apus apus and Haematopus ater as out-groups. Our results indicated that the mtDNA genome of F. naumanni includes 17,370 base pairs in length, which has the similar organization and gene order with other mtDNA genomes of the species belonging to Falconiformes. Further phylogenetic analyses supported that the F. naumanni clustered with other species of Falconidae, which formed the sister group of Accipitridae, Cathartes aura located at the basal position with Haematopus ater. In addition, Pandion haliaetus was clustered with other species of Accipitridae, which was conflict with the traditional classification system by taking P. haliaetus as an independent Familia of Falconidae.