RESUMO
Malnutrition is a risk factor of adverse clinical outcome in patients with cancer. Recent studies suggest that geriatric nutritional risk index (GNRI) could reflect the nutritional status in patients with various clinical conditions. The aim of the systematic review and meta-analysis was to evaluate the association between GNRI and survival of patients with hepatocellular carcinoma (HCC). Observational studies evaluating the association between pretreatment GNRI and survival of patients with HCC were obtained by search of PubMed, Web of Science, Embase, Wanfang, and CNKI databases. A random-effects model was used to pool the results after incorporating the potential influence of heterogeneity. Seven cohort studies including 2636 patients with HCC contributed to the meta-analysis. Pooled results showed that HCC patients with low pretreatment GNRI were associated with poor overall survival [hazard ratio (HR): 1.77, 95% confidence interval (CI): 1.32 to 2.37, p<0.001; I2=66%) and progression-free survival (HR: 1.62, 95% CI: 1.39 to 1.89, p<0.001; I2=0%) as compared to those with normal GNRI. Sensitivity analyses by excluding one study at a time showed similar results (p all<0.05). Subgroup analyses showed that the association between low pretreatment GNRI and poor survival of patients with HCC was not significantly affected by age of the patients, main treatment, cutoff of GNRI, or the follow-up durations. In conclusion, malnutrition indicated by a low pretreatment GNRI may be a risk factor of poor survival of patients with HCC.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Desnutrição , Humanos , Idoso , Avaliação Nutricional , Medição de Risco , Prognóstico , Estado Nutricional , Desnutrição/complicações , Fatores de Risco , Avaliação Geriátrica/métodos , Estudos RetrospectivosRESUMO
BACKGROUND: Thyroid carcinoma (THCA) is a common malignancy of the endocrine system. Further understanding of the molecular mechanism underlying THCA is crucial to develop effective diagnostic therapy and improve its treatments. In this study, we intended to provide novel direction for THCA targeted therapy from the aspect of lncRNA-miRNA-mRNA interaction. We aimed to investigate the function and molecular mechanism of lncRNA ATP1A1-AS1 in THCA. METHODS: Gene expression was assessed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Cell growth was detected by CCK-8 and EdU assays. Flow cytometry was applied for analyzing cell apoptosis. The binding of ATP1A1-AS1 or IRF2BP2 to miR-620 was validated by RNA pulldown and luciferase reporter assays. The protein levels were examined by western blotting. RESULTS: ATP1A1-AS1 was decreased in THCA cells and tissues. ATP1A1-AS1 overexpression attenuated cell growth and promoted apoptosis. MiR-620, which was upregulated in THCA, was identified as a direct target of ATP1A1-AS1. Furthermore, IRF2BP2 was discovered to be a target of miR-620, which displayed low expression in THCA cells and tissues. Importantly, IRF2BP2 knockdown reversed the influence of ATP1A1-AS1 overexpression on THCA cell proliferation and apoptosis. CONCLUSIONS: LncRNA ATP1A1-AS1 inhibited cell growth and promotes apoptosis in THCA via the miR-620/IRF2BP2 axis.
Assuntos
MicroRNAs , RNA Longo não Codificante , Neoplasias da Glândula Tireoide , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Linhagem Celular Tumoral , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias da Glândula Tireoide/genética , Proliferação de Células/genética , Apoptose/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , ATPase Trocadora de Sódio-Potássio/genética , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
Thyroid carcinoma (THCA) has been increasing in incidence greater than other cancers. Long noncoding RNAs (lncRNAs) were reported to play crucial roles in THCA development. Our study aimed to explore the underlying mechanism of lncRNA thymidylate synthetase opposite strand RNA (TYMSOS) in THCA. TYMSOS and myristoylated alanine rich protein kinase C substrate like 1 (MARCKSL1) were upregulated whereas miR-130a-5p was downregulated in THCA cells and tissues. The results of loss-of-function assays showed that TYMSOS knockdown inhibited cell metastasis and epithelial-mesenchymal transition (EMT) in THCA. TYMSOS was primarily distributed in the cytoplasm of THCA cells, as shown by FISH assay. RNA pulldown and luciferase reporter assay further showed that TYMSOS binds with miR-130a-5p. Luciferase reporter assay also revealed that MARCKSL1 is targeted by miR-130a-5p. Rescue assay showed that the suppression of TYMSOS downregulation on THCA cell malignant behaviors was reversed by MARCKSL1 overexpression. Additionally, overexpressing MARCKSL1 offset the inhibition of TYMSOS downregu-lation on the PI3K/Akt signaling pathway. TYMSOS knockdown inhibits the growth of THCA tumors, as in vivo assays showed. Collectively, TYMSOS facilitates THCA progression by sponging miR-130a-5p and upregulating MARCKSL1 to activate the PI3K/Akt signaling pathway, providing new avenues for THCA treatment.