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N6-methyladenosine (m6A) is the most pervasive RNA modification in eukaryotic cells. The dynamic and reversible m6A modification of RNA plays a critical role in the occurrence and progression of tumors by regulating RNA metabolism, including translocation, mRNA stability or decay, pre-mRNA splicing, and lncRNA processing. Numerous studies have shown that m6A modification is involved in the development of various cancers. This review aims to summarize the significant role of m6A modification in the proliferation and tumorigenesis of CRC, as well as the potential of modulating m6A modification for tumor treatment. These findings may offer new therapeutic strategies for clinical implementation of m6A modification in CRC in the near future.
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N6-methyladenosine (m6a)-related mRNAs and lncRNAs have been explored for their functions in several cancers. The present study aimed to identify potential signatures of m6a-related lncRNAs in hepatocellular carcinoma (HCC). We downloaded the expression and clinical data from The Cancer Genome Atlas (TCGA) database. The interacted mRNAs and lncRNAs, prognosis-related lncRNAs, potential metabolic pathways of lncRNAs, immune infiltration of various cells, and CD274 (PD-L1) -related lncRNAs were analyzed. Then, in vitro experiments explored the role of AC012073.1 (LOC105377626) in HCC cell lines. We found that candidate 14 lncRNA signatures play functions in HCC maybe by affecting immune infiltration, cell cycle, Notch signaling pathway, etc. LncRNA AC012073.1 (LOC105377626) functions as oncogenic roles in affecting HCC prognosis.
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Liver cancer is the fifth most common malignant tumor in terms of incidence and the third leading cause of cancer-related mortality globally. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. Although great progress has been made in surgical techniques, hepatic artery chemoembolization, molecular targeting and immunotherapy, the prognosis of liver cancer patients remains very poor. N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotic cells and regulates various stages of the RNA life cycle. Many studies have reported that the abnormal expression of m6A-related regulators in HCC represent diagnostic and prognostic markers and potential therapeutic targets. In this review, firstly, we introduce the latest research on m6A-related regulators in detail. Next, we summarize the mechanism of each regulator in the pathogenesis and progression of HCC. Finally, we summarize the potential diagnostic, prognostic and therapeutic value of the regulators currently reported in HCC.
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BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. N6-methyladenosine (m6A) RNA methylation is dynamically regulated by m6A RNA methylation modulators ("writer," "eraser," and "reader" proteins), which are associated with cancer occurrence and development. The purpose of this study was to explore the relationships between m6A RNA methylation modulators and HCC. METHODS: First, using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we compared the expression levels of 13 major m6A RNA methylation modulators between HCC and normal tissues. Second, we applied consensus clustering to the expression data on the m6A RNA methylation modulators to divide the HCC tissues into two subgroups (clusters 1 and 2), and we compared the clusters in terms of overall survival (OS), World Health Organization (WHO) stage, and pathological grade. Third, using least absolute shrinkage and selection operator (LASSO) regression, we constructed a risk signature involving the m6A RNA methylation modulators that affected OS in TCGA and ICGC analyses. RESULTS: We found that the expression levels of 12 major m6A RNA methylation modulators were significantly different between HCC and normal tissues. After dividing the HCC tissues into clusters 1 and 2, we found that cluster 2 had poorer OS, higher WHO stage, and higher pathological grade. Four m6A RNA methylation modulators (YTHDF1, YTHDF2, METTL3, and KIAA1429) affecting OS in the TCGA and ICGC analyses were selected to construct a risk signature, which was significantly associated with WHO stage and was also an independent prognostic marker of OS. CONCLUSIONS: In summary, m6A RNA methylation modulators are key participants in the malignant progression of HCC and have potential value in prognostication and treatment decisions.
Assuntos
Carcinoma Hepatocelular/patologia , Perfilação da Expressão Gênica/métodos , Neoplasias Hepáticas/patologia , Metiltransferases/genética , Proteínas de Ligação a RNA/genética , Adenosina/análogos & derivados , Adenosina/metabolismo , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Gradação de Tumores , Prognóstico , Análise de Sequência de RNA/métodosRESUMO
Cytotoxin-associated gene A (CagA) is one of the most important virulence factors of Helicobacter pylori, and serves a role in H. pylorimediated tumorigenesis in gastric cancer. However, the underlying molecular mechanism remains to be elucidated. The present study aimed to investigate the effects of CagA on the proliferation and apoptosis of GES1 cells, and the underlying mechanism. A CagA eukaryotic expression plasmid was constructed and transfected into GES1 cells. The mRNA and protein levels of CagA, tumor necrosis factor receptorassociated factor 1 (TRAF1) and tumor necrosis factor receptor superfamily member 9 (41BB) were determined using the reverse transcriptionquantitative polymerase chain reaction and western blot analysis, respectively. Western blot and ELISA analysis was used to detect the release of interleukin (IL)8. An MTT assay and flow cytometric analysis was used to assess cell viability and apoptosis, respectively. Ectopic expression of CagA markedly increased TRAF1 and 41BB mRNA and protein levels in GES1 cells. CagA increased the expression and release of IL8 in GES1 cells. The expression of CagA significantly promoted the proliferation (P<0.05) and inhibited the apoptosis (P<0.05) of GES1 cells. In conclusion, CagA upregulated TRAF1/41BB, thereby promoting the proliferation and inhibiting the apoptosis of GES-1 cells.
Assuntos
Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/metabolismo , Fator 1 Associado a Receptor de TNF/genética , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Antígenos de Bactérias/genética , Apoptose , Proteínas de Bactérias/genética , Linhagem Celular , Proliferação de Células , Expressão Ectópica do Gene , Regulação da Expressão Gênica , Infecções por Helicobacter , Helicobacter pylori , Humanos , Interleucina-8/genética , Interleucina-8/metabolismo , Fator 1 Associado a Receptor de TNF/metabolismo , Transfecção , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismoRESUMO
OBJECTIVE: To investigate the correlation between certain unhealthy lifestyles and the incidence of gastroesophageal reflux disease (GERD), thus to provide the lifestyle guidelines for GERD patients.â© Methods: Retrospective study were conducted for 402 GERD and 276 non-GERD out-patients in Department of Gastroenterology, Third Xiangya Hospital, Central South University from August, 2014 to August, 2015 based on questionnaire survey, then the correlation of unhealthy lifestyles with GERD were analyzed.â© Results: The top 10 common symptoms for GERD were as follows: reflux, acid regurgitation, postprandial fullness, heartburn, swallow obstruction or pain, epigastric burning sensation, paraesthesia pharynges, poststernal pain, chronic laryngopharyngitis, and chronic cough. The top 8 unhealthy habits closely related to GERD were as follows: fast-eating, over-eating, spicy preferred diet, sweets preferred diet, anxious, soup preferred diet, high-fat diet, and hot eating. Single-factor analysis showed that GERD was markedly correlated to gender (male), age (≥60 years), BMI, smoking, alcohol, fast-eating, over-eating, hot-eating, spicy preferred diet, high-fat diet, acid preferred diet, sweets preferred diet, hard food preference, strong tea preference, coffee preference, immediately on bed after meal, difficult defecation, dyscoimesis, anxious, and too tight belt, respectively (P<0.05). Logistic multiple regression analysis indicated that the largest risk factor for GERD was the fast-eating (OR=3.214, 95% CI 2.171 to 4.759, P<0.001) followed by the over-eating (OR=2.936, 95% CI 1.981 to 4.350, P<0.001), elderly population (OR=2.047, 95% CI 1.291 to 3.244, P=0.002), too tight belt (OR=2.003, 95% CI 1.013 to 3.961, P=0.046), and hot-eating (OR=1.570, 95% CI 1.044 to 2.362, P=0.030).â© Conclusion: The elderly people are at high risk for GERD, and unhealthy habits like fast-eating, over-eating, too tight belt, and hot-eating is closely related to GERD. The lifestyles such as chewing food thoroughly, splitting the meals up, warm and cool diet, keeping patients out of the too tight belt are necessary for GERD patients.
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Refluxo Gastroesofágico/epidemiologia , Estilo de Vida , Idoso , Consumo de Bebidas Alcoólicas/efeitos adversos , Doces/efeitos adversos , Dieta Hiperlipídica/efeitos adversos , Comportamento Alimentar , Feminino , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/etiologia , Temperatura Alta/efeitos adversos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Fumar/efeitos adversos , Especiarias/efeitos adversos , Inquéritos e Questionários , Avaliação de SintomasRESUMO
Objective. CagA+/vacAs1+/vacAm1+ Helicobacter pylori upregulates the expression of tumor necrosis factor receptor-associated factor 1 (TRAF1), tumor necrosis factor receptor superfamily member 9 (4-1BB), and B-cell lymphoma-extra large (Bcl-xL) in human gastric epithelial cells. We investigated the correlation between cagA/vacAs1/vacAm1 and TRAF1/4-1BB/Bcl-xL expression in gastric mucosal tissue of patients with gastric disorders. Methods. We collected gastric mucosa samples from 35 chronic, nonatrophic gastritis (CG) patients, 41 atrophic gastritis patients, 44 intestinal metaplasia with atypical hyperplasia (IM) patients, and 28 gastric carcinoma (Ca) patients. The expression of TRAF1, 4-1BB, and Bcl-xL was determined using western blotting. The expression of cagA, vacAs1, and vacAm1 in H. pylori was examined with polymerase chain reaction. Results. The expression of TRAF1, 4-1BB, and Bcl-xL was significantly upregulated in IM and Ca patients (P < 0.05 compared with CG). There were more cases of cagA+/vacAs1+/vacAm1+ H. pylori infection in samples with elevated TRAF1, 4-1BB, or Bcl-xL expression (P < 0.05). Additionally, there were a remarkably large number of samples with upregulated TRAF1/4-1BB/Bcl-xL expression in cases of cagA+/vacAs1+/vacAm1+ H. pylori infection (44 cases, 67.7%; P < 0.05). Conclusions. The pathogenesis of IM and Ca may be promoted by cagA+/vacAs1+/vacAm1+ H. pylori, possibly via upregulated TRAF1, 4-1BB, and Bcl-xL in gastric mucosal tissue.