ABSTRACT
BACKGROUND: The purpose of this study was to investigate the specific effects of signal transducer and activator of transcription 4 (STAT4)-induced long intergenic nonprotein coding RNA 1278 (LINC01278) on the growth of non-small cell lung cancer (NSCLC) cells involved in the microRNA (miR)-877-5p/activated transcription factor 4 (ATF4) axis. METHODS: NSCLC tumor tissue and adjacent normal tissue were collected. Human normal lung epithelial cell BEAS-2B and human NSCLC cell lines (H1299, H1975, A549, H2228) were collected. The expression levels of STAT4, LINC01278, miR-877-5p, and ATF4 were detected. A549 cells were screened for subsequent experiments. The proliferation ability of cells was detected by colony formation experiment. Cell apoptosis was tested by flow cytometry. Scratch test and transwell assay were used to detect the migration and invasion ability of cells. Biological function of LINC01278 in NSCLC was confirmed by xenograft experiments. RESULTS: Low expression miR-877-5p and high expression of STAT4, LINC01278 and ATF4 were detected in NSCLC. Silenced LINC01278 in A549 cell depressed cell proliferation, migration and invasion, but facilitated cell apoptosis. LINC01278 was positively correlated with STAT4 and could directly bind to miR-877-5p. Upregulating miR-877-5p suppressed NSCLC cell progression, while downregulating miR-877-5p had the opposite effect. Upregulating miR-877-5p abrogated the effects of silenced LINC01278 on NSCLC cell progression. MiR-877-5p targeted ATF4. ATF4 upregulation could partly restore the carcinogenic effect of LINC01278 in vitro and in vivo. CONCLUSION: Our data supports that STAT4-induced upregulation of LINC01278 promotes NSCLC progression by modulating the miR-877-5p/ATF4 axis, suggesting a novel direction for NSCLC treatment.
Subject(s)
Activating Transcription Factor 4 , Carcinoma, Non-Small-Cell Lung , Cell Proliferation , Gene Expression Regulation, Neoplastic , Lung Neoplasms , MicroRNAs , RNA, Long Noncoding , STAT4 Transcription Factor , Up-Regulation , Humans , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Activating Transcription Factor 4/metabolism , Activating Transcription Factor 4/genetics , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Animals , STAT4 Transcription Factor/metabolism , STAT4 Transcription Factor/genetics , Neoplasm Invasiveness , Cell Line, Tumor , A549 Cells , Mice, Nude , Mice , Apoptosis , Female , Male , Cell Movement , Mice, Inbred BALB CABSTRACT
Obstructive sleep apnea (OSA) usually leads to the occurrence of diabetes. Gestational diabetes mellitus (GDM) is a common gestational complication associated with adverse maternal and fetal outcomes. Increasing studies suggest that women with OSA during pregnancy may be at a significantly greater risk of developing GDM. It is crucial to explore the association between OSA and GDM and the mechanisms underlying this association. In this review, we presented a comprehensive literature review of the following: the association between OSA and GDM, the possible mechanisms of this association, and the effects of continuous positive airway pressure (CPAP) on OSA with GDM. The results showed that most authors suggested that there was an association between OSA and GDM. The intermittent hypoxemia (IH) and reduction of slow-wave sleep (SWS) may be the key to this association. IH induces the products of oxidative stress and inflammation as well as dysregulation of the hypothalamic-pituitary-adrenal, which lead to diabetes. In addition, SWS reduction in OSA enhances the inflammation by increasing the inflammatory cytokines, increases the sympathetic activation, and causes changes in leptin level, which result in the development of GDM. Additionally, whether CPAP is beneficial to GDM remains still unclear.
Subject(s)
Diabetes, Gestational , Pregnancy Complications , Sleep Apnea, Obstructive , Pregnancy , Female , Humans , Diabetes, Gestational/etiology , Pregnancy Complications/etiology , Risk Factors , Inflammation/complications , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/therapy , Sleep Apnea, Obstructive/epidemiologyABSTRACT
Poor prognosis in patients with glioma is primarily due to rapid tumor growth and cell invasion and migration. In addition, microRNA (miR)27b is decreased in metastatic glioma. The present study investigated whether sevoflurane inhibited glioma cell progression by targeting miR27b. Cell proliferation was analyzed using a Cell Counting Kit8 assay and a wound healing assay was used to detect cell migration. Western blotting and reverse transcriptionquantitative PCR analysis were performed to determine the protein and mRNA expression levels. A dual luciferase assay was used to determine the relationship between vascular epithelial growth factor (VEGF) and miR27b. VEGF was identified to be a direct target of miR27b. Moreover, sevoflurane treatment increased the expression of miR27b and decreased the expression of VEGF in U251 and U87 cells. Compared with the control group, sevoflurane inhibited the proliferation and migration of U251 and U87 cells, as well as the expression of matrix metalloproteinase (MMP)2 and MMP9, which were subsequently abolished by pretreatment with an miR27b inhibitor. The present results indicated the potential use of sevoflurane by anesthesiologists for the surgical resection of glioma, which may improve patient outcomes in the clinical setting.
Subject(s)
Antineoplastic Agents/pharmacology , Cell Movement/drug effects , Cell Proliferation/drug effects , Glioma/metabolism , Sevoflurane/pharmacology , Cell Line , Cell Line, Tumor , Humans , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/metabolismABSTRACT
BACKGROUND: Lung adenocarcinoma (LUAD) is a major type of NSCLC and has high morbidity and mortality. The identification of useful prognostic biomarkers for LUAD is important. CBX7 has been reported in various cancers yet its expression level and potential roles have not been fully understood. METHODS: GEPIA, Oncomine, TCGA, KM plotter and OSluca databases were used to explore the expression profile and prognostic effects of CBX7 mRNA expression in patients with LUAD. TIMER was used to explore the relationship between CBX7 and immune infiltrating cells. GSEA was used to further explore the potential biological process and pathways regulated by CBX7 in LUAD. Lastly, IHC detection of CBX7 in 95 samples was used to validate the result. RESULTS: We found CBX7 was downregulated in LUAD in GEPIA, Oncomine and TCGA databases. TCGA, KM plotter and OSluca databases suggested that CBX7 was associated with poor clinical outcomes and low survival rate. Using TIMER, we found that CBX7 might be associated with immune infiltration. Via gene set enrichment analysis, we found that tumor-associated biological processes and signaling pathways were enriched in the CBX7 downregulated group. Using clinical samples, we found that CBX7 protein has low expression in LUAD and was associated with poor survival. CONCLUSION: CBX7 might serve as a promising biomarker and potential molecular target in LUAD.
