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Cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) is a newly identified cytosolic DNA sensor, but its function in lung epithelial cells is relatively unknown. In the present study, the effects of lipopolysaccharide (LPS) on the expression and function of cGAS in the A549 lung epithelial cell line was investigated. The cells were treated with LPS at different concentrations (e.g., 100, 200, 400 and 800 ng/ml), and the cGAS expression levels were examined via western blot analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The cells were pretreated with LPS, followed by E. coli DNA transfection using Lipofectamine® 3000. After 24 h, interferon (IFN)-β production was measured using ELISA and the expression of the autophagic markers, microtubule-associated proteins 1A/1B light chain 3 and sequestosome-1, were determined using western blot analysis. The cells were also pretreated with either a toll-like receptor (TLR) 4 inhibitor, a serine/threonine-protein kinase TBK1 (TBK1) inhibitor or an nuclear factor (NF)-κB inhibitor, followed by LPS treatment, and the cGAS expression levels were examined via western blot analysis and RT-qPCR. The result showed that LPS treatment upregulated cGAS expression in a dose-dependent manner. E. coli DNA treatment could induce IFN-β production and autophagy via cGAS, which was enhanced by LPS pretreatment. The effect of LPS on cGAS expression was suppressed by treatment with a TLR4 inhibitor, a TBK1 inhibitor and an NF-κB inhibitor. In conclusion, LPS enhances DNA-induced IFN-β production and autophagy by upregulating cGAS expression through the myeloid differentiation primary response protein MyD88-independent TLR4 signaling pathway in A549 cells. [ABSTRACT FROM AUTHOR]

A previous study revealed that DEP domain containing 1 (DEPDC1) is involved in the carcinogenesis of bladder cancer via forming a complex with zinc finger protein 224 (ZNF224) to suppress A20 expression, resulting in the activation of the nuclear factor (NF)-κB signaling pathway; however, the role of DEPDC1 in liver cancer remains unclear. Hep G2 cells were treated with 11R-DEP: 611–628, a peptide capable of disrupting the DEPDC1-ZNF224 complex. Cell proliferation was examined using an MTT assay and apoptosis was analyzed via detection of the apoptotic marker caspase-3 using western blot analysis. A20 expression was examined via reverse transcription-quantitative polymerase chain reaction and NF-κB subcellular localization was determined via immunofluorescence staining. microRNA (miR)-130a was overexpressed in HepG2 cells and its effects on proliferation and apoptosis were examined. The results demonstrated that 11R-DEP: 611–628 (3 µM) and miR-130a inhibited cell proliferation and promoted apoptosis in HepG2 cells by activating A20 expression, which blocks the nuclear transportation of NF-κB. In addition, the results demonstrated that the 11R-DEP: 611–628 (3 µM) treatment resulted in downregulation of DEPDC1 expression, indicating that DEPDC1 expression is regulated by the DEPDC1-ZNF224 complex. In conclusion, the data indicated that DEPDC1 suppresses apoptosis to promote cell proliferation through the NF-κB signaling pathway in HepG2 cells and that DEPDC1 is a potential target for the treatment of liver cancer. [ABSTRACT FROM AUTHOR]

The ectopic expression of insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has been demonstrated to facilitate tumorigenesis and induce proliferation in a various types of cancer. However, the role of IGF2BP2 in esophageal squamous cell carcinoma (ESCC) has yet been fully elucidated. In this regard, the current study assessed the expression patterns and clinical significance of IGF2BP2 in 94 Chinese patients diagnosed with ESCC. Immunohistochemistry and reverse transcription-quantitative PCR assays were employed to assess IGF2BP2 expression in ESCC tissues compared with adjacent healthy tissues. The results revealed that the protein expression of IGF2BP2 was substantially upregulated in ESCC tissues compared with adjacent ESCC tissues. More specifically, higher IGF2BP2 expression strongly associated with tumor node metastasis stage, lymphatic infiltration and lymph node metastasis. Using two ESCC cell lines (TE-1 and TE-10), the inhibition of IGF2BP2 expression by small interfering RNA was proven to induce apoptosis and suppress proliferation, migration and cell cycle progression in vitro. Collectively, the present findings indicated that IGF2BP2 may serve a major role in the development of ESCC carcinogenesis. The present study may be helpful in the design of potential drug targets in the treatment of ESCC. [ABSTRACT FROM AUTHOR]

The NICE-3 protein serves an oncogenic role in hepatocellular carcinoma, but its role in lung adenocarcinoma (LUAD) remains unknown. The aim of the present study was to investigate the potential role and underlying mechanisms of NICE-3 in LUAD. In the present study, NICE-3 expression in LUAD tissues and its association with patient prognosis were analyzed using datasets from The Cancer Genome Atlas and Gene Express Omnibus. After NICE-3-knockdown with small interfering RNA in LUAD cells, cell proliferation was measured by cell counting, cell cycle was examined by flow cytometry, cell invasion and migration were detected by Transwell assays and autophagic markers LC3 and p62, as well as phosphorylation of S6K and AKT, were determined by western blotting. The results of public database analysis demonstrated that compared with normal lung tissues, NICE-3 expression was increased in LUAD tissues, where high expression levels were associated with a poor prognosis. The results of in vitro experimentation in LUAD cells indicated that NICE-3-knockdown inhibited proliferation, cell cycle, migration and invasion, but enhanced autophagy. Notably, NICE-3-knockdown inhibited AKT/mTORC1 signaling. The present results suggested that NICE-3 may serve an oncogenic role in LUAD via the AKT/mTORC1 signaling pathway and may therefore be a potential therapeutic target for LUAD. [ABSTRACT FROM AUTHOR]

Melanocyte proliferating gene 1 (MYG1) is an exonuclease that participates in RNA processing and is required for normal mitochondrial function. However, its role in tumorigenesis remains unknown. The present study aimed to investigate the role of MYG1 and its underlying mechanisms in human lung adenocarcinoma (LUAD). The expression levels of MYG1 in tumor tissues of patients with LUAD were obtained from public cancer databases and analyzed using the UALCAN online software. The association between MYG1 expression levels and the prognosis of patients with LUAD was analyzed using the Kaplan-Meier plotter. In addition, the role of MYG1 in the LUAD A549 and H1993 cell lines was determined by knocking down MYG1 expression with a specific small interfering RNA or by overexpressing it with a MYG1-containing plasmid. The results demonstrated that MYG1 expression levels were upregulated in LUAD tissues compared with those in normal lung tissues from healthy subjects, and high MYG1 expression levels were associated with an unfavorable prognosis. MYG1 promoted the proliferation, migration and invasion of A549 and H1993 cells. In addition, MYG1 inhibited autophagy via the AMP-activated protein kinase/mTOR complex 1 signaling pathway. Collectively, the present results suggested that MYG1 may serve an oncogenic role in LUAD and may be a potential therapeutic target for LUAD. [ABSTRACT FROM AUTHOR]

Methyltransferase-like 1 (METTL1) is a transfer RNA and microRNA modifying enzyme. However, its role in lung adenocarcinoma (LUAD) remains unknown. The present study aimed to investigate the effect of METTL1 in LUAD and determine the association between METTL1 expression and prognosis of patients with LUAD. The expression profile of METTL1 in LUAD tissues was downloaded from public cancer databases and analyzed using the Gene Expression Profiling Interactive Analysis database and UALCAN online software. In addition, the association between METTL1 expression and prognosis of patients with LUAD was assessed using the Kaplan-Meier Plotter software. The effect of METTL1 in the A549 cell line was determined in vitro via overexpression and knockdown experiments. The results demonstrated that METTL1 was upregulated in LUAD tissues, and its increased expression was associated with unfavorable prognosis. Furthermore, METTL1 promoted proliferation and colony formation of A549 cells, and inhibited autophagy via the AKT/mechanistic target of rapamycin complex 1 signaling pathway. Taken together, the results of the present study suggest that METTL1 acts as an oncogene in LUAD, thus may be a potential prognostic predictor and therapeutic target for LUAD. [ABSTRACT FROM AUTHOR]