In a meta-analysis, the long noncoding RNA cancer susceptibility candidate 8 (CASC8) was found to be a cancer susceptibility gene closely related to lung cancer, but its functions in lung cancer are unknown. In the Cancer Genome Atlas database, the expression of CASC8 was significantly higher in non-small cell lung cancer than in adjacent normal tissues, and high expression of CASC8 was associated with poor prognosis in patients with lung adenocarcinoma. Silencing CASC8 inhibited proliferation, migration, and invasion in non-small cell lung cancer cell lines. Silencing CASC8 also promoted sensitivity to osimertinib through Forkhead box M1 (FOXM1). Therefore, this pathway can be exploited in patients with lung cancer resistant to targeted therapies. Our study revealed for the first time that silencing CASC8 inhibited the proliferation, migration, and invasion of non-small cell lung cancer cells and promoted their sensitivity to osimertinib, suggesting that CASC8 is closely related to the occurrence and development of non-small cell lung cancer. This may provide insight into mechanisms of treatment for non-small cell lung cancer.
BackgroundLymph node metastasis is one of the most important factors affecting the prognosis of tongue cancer, and the molecular mechanism regulating lymph node metastasis of tongue cancer is poorly known.MethodsThe gene expression dataset GSE2280 and The Cancer Genome Atlas (TCGA) tongue cancer dataset were downloaded. R software was used to identify the differentially expressed hallmark gene sets and individual genes between metastatic lymph node tissues and primary tongue cancer tissues, and the Kaplan–Meier method was used to evaluate the association with overall survival. The screening and validation of functional genes was performed using western blot, q-PCR, CCK-8, migration and invasion assays, and lymphangiogenesis was examined by using a tube formation assay.ResultsThirteen common hallmark gene sets were found based on Gene Set Variation Analysis (GSVA) and then subjected to differential gene expression analysis, by which 76 deregulated genes were found. Gene coexpression network analysis and survival analysis further confirmed that IER3 was the key gene associated with the prognosis and lymph node metastasis of tongue cancer patients. Knockdown of IER3 with siRNA inhibited the proliferation, colony formation, migration and invasion of Tca-8113 cells in vitro and it also inhibited the secretion and expression of VEGF-C in these cells. The culture supernatant of Tca-8113 cells could promote lymphangiogenesis and migration of lymphatic endothelial cells, and knockdown of IER3 in Tca-8113 cells suppressed these processes.ConclusionOur study demonstrated that IER3 plays important roles in lymphangiogenesis regulation and prognosis in tongue cancer and might be a potential therapeutic target.
Background: Dentition defect is a common symptom in clinical dental patients. This study compared the clinical effects of denture restoration and dental implant restoration in the treatment of dentition defects through meta-analysis.Methods: Data retrieval was conducted through the PubMed, Web of Science, Embase, CNKI, and Wanfang databases. A total of 479 related literatures published in English or Chinese from 2013 to 2020 were included. Literature screening, data extraction and comprehensive evaluation, and analysis by metaanalysis was performed by 3 authors.Results: A total of 17 studies and 1,459 patients were included. Among the 17 studies, the effective rate of treatment between the two groups was compared and the experimental group rate was significantly higher than that of the control group [odds ratio (OR) =6.149, 95% confidence interval (CI): 4.103-9.215, P<0.001]; the mastication function score was compared, and was higher in the experimental group than in the control group [standardized mean difference (SMD) =1.632, 95% CI: 1.039-2.224, P<0.001]; the retention function score was compared, and was higher in the experimental group than in the control group (SMD =1.775, 95% CI: 1.095-2.455), P<0.001); the aesthetics score was also compared, and was higher in the experimental group than in the control group (SMD =1.300, 95% CI: 0.499-2.100, P=0.001). Among 17 studies, 15 compared the comfort score, which was higher in the experimental group than in the control group (SMD =1.357, 95% CI: 0.455-2.258, P=0.003).Conclusions: Compared with denture restoration, dental implant restoration is more effective in the treatment of dentition defect with a higher comprehensive score of functional restoration.
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Background The expression of Kelch-like protein 18 (KLHL18) in non-small cell lung cancer (NSCLC) is lower than that in normal lung tissue according to the Gene Expression Profiling Interactive Analysis database. KLHL18 is a BTB domain protein and binds cullin 3 (CUL3). However, whether this complex participates in ubiquitination-mediated protein degradation in NSCLC is unclear. Therefore, we aimed to investigate the role of KLHL18 in human NSCLC cells. Results We found that KLHL18 is downregulated in cancer cells and is associated with poor prognosis. Further, its expression was significantly associated with tumor node metastasis (TNM) stage, lymph node metastasis, and tumor size. In vitro analysis of NSCLC cells showed that overexpressing KLHL18 inhibited cell proliferation, migration, and invasion. We found that the tumor-inhibitory effect of the KLHL18 protein was achieved by promoting the ubiquitination and degradation of phosphatidylinositol 3-kinase (PI3K) p85α and inhibiting the expression of PD-L1 protein, ultimately preventing tumor cell immune escape. Conclusions Our results identified the tumor-suppressive mechanism of KLHL18 and suggested that it is closely related to NSCLC occurrence and development. Further investigation of the underlying mechanism may provide new targets for NSCLC treatment.
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