NAT10 Promotes Malignant Progression of Lung Cancer via the NF-κB Signaling Pathway.

BACKGROUND: NAT10 (N-acetyltransferase 10) is a newly identified novel acetyltransferase. Abnormal expression of NAT10 is associated with several human disorders, including cancer, autoimmune diseases, and cardiovascular disease. This study aimed to investigate the role of NAT10 in promoting lung cancer malignant progression through the NF-κB (nuclear factor κB) signaling pathway. METHODS: Cells lines BEAS-2B, NCI-H524, A549, PC-9, NCI-H23, and NCI-H258 were cultured for identification. Western blotting and PCR assays determined gene expression within the sample cells. Cellular functionality was assayed using CCK8 (Cell Counting Kit-8), Dual-Luciferase Reporter, and Colony formating. RESULTS: The PCR assay and Western blotting showed a significant elevation of NAT10 levels within tumor tissues compared to paraneoplastic tissues (p < 0.05). Specifically, NAT10 only affected the expression and content of RelA/p65 in lung cancer. Analysis from the TCGA (The Cancer Genome Atlas) database indicated that elevated expression levels of NAT10 in tumors can be a good prognostic indicator for lung cancer patients. The CCK8 assay showed that the knockdown of NAT10 significantly suppressed the A549 cells' progression rate (p < 0.05). The colony formation assays further confirmed that the overexpression of NAT10 significantly increased the generation of clones in the NCI-H524 cells (p < 0.05). The proliferation rate influenced by the overexpression of NAT10 was inhibited by blocking the NF-κB signaling pathway (p < 0.05). Dual-luciferase reporter gene assay results revealed NAT10's potential in promoting the NF-κB signaling pathway's activity in lung cancer. Immunohistochemical staining underscored a strong link between NAT10 protein expression and the NF-κB signaling pathway in lung cancer tissues. CONCLUSIONS: NAT10's expression is significantly upregulated in tumor tissues, supported by PCR results. NAT10 plays a role in the development and proliferation of lung cancer cells and can activate the NF-κB signaling pathway in lung cancer. Hence, NAT10's regulation of the NF-κB signaling pathway is critical in the malignant proliferation of lung cancer.

The Treatment for a Patient with Cancer of Unknown Primary: A Case Report.

BACKGROUND: Cancer of unknown primary (CUP) is metastatic at diagnosis with an unknown primary site, indicating a high degree of malignancy with a poor prognosis. The development and application of targeted therapy and immunotherapy are current research hotspots, which provide additional treatment options for CUP. CASE PRESENTATION: A 36-year-old male presented with pain on the right hip in April 2018. After various examinations, he was diagnosed with CUP. This patient received chemotherapy, immunotherapy, and local radiotherapy in our department. However, the use of radiotherapy after immunotherapy resulted in severe pneumonia. CONCLUSION: Compared with traditional treatments, immunotherapy is an effective treatment with fewer side effects and better patient tolerance. However, treating physicians should be still pay special attention to the occurrence of side effects when radiotherapy is combined with immunotherapy.

Expression and Clinical Value of LncRNA GAPLINC in Esophageal Squamous Cell Carcinoma.

BACKGROUND: The long noncoding RNA (lncRNA) GAPLINC, or gastric adenocarcinoma predictive long intergenic ncRNA, plays a carcinogenic role in a variety of different tumor types. There is limited information regarding the biological function of GAPLINC in the development of esophageal squamous cell carcinoma (ESCC). METHODS: Surgical tissue samples of 40 patients undergoing ESCC radical surgery were collected, including ESCC tissues and corresponding adjacent normal tissues. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of lncRNA GAPLINC in the human ESCC cell line (TE11). The function role of LncRNA GAPLINC was detected after specific siRNA interference and overexpression in the TE11 cell line. The effects of LncRNA GAPLINC on ESCC cell proliferation, migration and invasion abilities were investigated by flow cytometry, using the Cell Counting Kit-8 (CCK-8), and by Transwell migration assays, respectively. RESULTS: The expression of lncRNA GAPLINC in ESCC tissues was significantly higher than that in corresponding adjacent normal tissues (P<0.05) and correlated with the degree of tumor differentiation (P<0.05). Compared with human esophageal normal epithelial cell lines, the expression of LncRNA GAPLINC was significantly higher in the human ESCC cell line (P<0.05). CCK-8 assays showed that LncRNA GAPLINC overexpression increased the growth rate of cells (P<0.05). Transwell experiments showed that LncRNA GAPLINC overexpression increased the ability of cell migration and invasion compared to control cells (P<0.05). Annexin V assay revealed that LncRNA GAPLINC silencing increased early stage apoptosis (P<0. 05). CONCLUSION: Our results suggest that LncRNA GAPLINC may be used as a biomarker for the diagnosis and monitoring of ESCC, and may play an oncogenic role in ESCC.

Annexin A1-mediated inhibition of inflammatory cytokines may facilitate the resolution of inflammation in acute radiation-induced lung injury.

The present study evaluated the role of annexin A1 (ANXA1) in the treatment of acute radiation-induced lung injury (RILI) and investigated the mechanism of its action. The expression of ANXA1, interleukin-6 (IL-6) and myeloperoxidase (MPO) in the plasma of patients with RILI prior to and following hormonotherapy was assessed by enzyme-linked immunosorbent assay. The association of plasma ANXA1 concentration with clinical effect, and the correlation between the expression of ANXA1 and that of IL-6 and MPO were evaluated. ANXA1 was overexpressed or knocked down in a macrophage cell line, and its impact on IL-6 and MPO expression was measured. Following glucocorticoid hormonotherapy, patients with RILI exhibited a higher plasma concentration of ANXA1 compared with that prior to treatment, while IL-6 and MPO levels were lower. The concentration of ANXA1 in plasma was negatively correlated with IL-6 and MPO levels, with a correlation coefficient of -0.492 and -0.437, respectively (P<0.001). The increasing concentration of ANXA1 in plasma following treatment was associated with the clinical effect in patients with RILI (P=0.007). The expression levels of of IL-6 and MPO were inhibited both in the cytoplasm and in the culture solution, when ANXA1 expression was upregulated in a macrophage cell line. In conclusion, ANXA1 inhibited the synthesis and secretion of IL-6 and MPO inflammatory cytokines, indicating that ANXA1 may have therapeutic potential as a treatment target for RILI.

Association of serum annexin A1 with treatment response and prognosis in patients with esophageal squamous cell carcinoma.

OBJECTIVE: Annexin A1 (ANXA1), a calcium-dependent phospholipid binding protein, is known to be regulated by microRNA-196a (miR-196a) in esophageal adenocarcinoma, and its high expression in tumor tissue is correlated with the poor prognosis of esophageal squamous cell carcinoma (ESCC). However, the role of ANXA1 in the serum of patients with ESCC remains unclear. MATERIALS AND METHODS: In this study, we used enzyme-linked immunosorbent assay to evaluate the levels of ANXA1 and real-time polymerase chain reaction to detect the expression of miR-196a in the serum of ESCC patients (healthy donors as controls) and evaluated the relationship between ANXA1 and clinical outcomes. RESULTS: The results showed that the level of serum ANXA1 in ESCC patients was significantly lower than that in controls (P = 0.001) but increased after chemoradiotherapy (P = 0.001). There was no correlation between the baseline level of serum ANXA1 and the short-term efficacy of treatment (P = 0.26) as well as the 1-year progression-free survival (PFS) (P = 0.094). However, there existed a significant correlation between the increases of serum ANXA1 expression and the 1-year PFS (P = 0.04). A higher increase (>2-fold of baseline) in the serum ANXA1 levels was correlated with a poorer PFS (hazard ratio = 3.096, 95% confidence interval 1.239-7.861). There was an inverse correlation between the expressions of miR-196a and ANXA1 in serum (Pearson's correlation of -0.54, P = 0.021). CONCLUSION: Our data revealed that the expression of serum ANXA1 in ESCC patients increases after chemoradiotherapy and the increased fold change in serum ANXA1 confers independent negative prognostic impact in ESCC. The higher the increase in serum ANXA1 levels, the poorer the outcome.

Diagnosis, clinicopathological characteristics and prognosis of pulmonary mucinous adenocarcinoma.

Primary pulmonary mucinous adenocarcinoma (PPMA) is an uncommon subtype of lung adenocarcinoma. The present study attempted to clarify the diagnosis, clinicopathological characteristics, and pathologic significance of epithelial growth factor receptor (EGFR) and Kirsten rat sarcoma viral oncogene (KRAS) mutations and the prognosis of PPMA. A total of 29 patients with PPMA from among 1,469 surgically resected patients with lung adenocarcinoma were enrolled. All of the tumours expressed CK7 and 5 cases exhibited co-expression with CK20. A total of 8 cases expressed EGFR, 14 cases expressed P53 and 2 cases expressed CEA. The majority of mucinous adenocarcinomas expressed thyroid transcription factor 1, Napsin A, Villin and Cam5.2 proteins. KRAS mutations were observed in 62% of patients and were more prevalent in the lower lung lobe and in patients with invasive mucinous adenocarcinoma. A total of 2 cases exhibited an EGFR mutation, and the co-mutation of KRAS and EGFR was only detected in 1 case. The relapse-free and overall survival rates at 5 years were 70.4, and 81.5%, respectively. The results may assist to identify a molecular target and supply important information for a therapeutic strategy for patients with PPMA.

Effect of Annexin A1 gene on the proliferation and invasion of esophageal squamous cell carcinoma cells and its regulatory mechanisms.

The aim of this study was to examine the effect of Annexin A1 (ANXA1) on the proliferation, migration and invasion of esophageal squamous cell carcinoma (ESCC) cells and its possible mechanisms of action. After constructing the ANXA1 overexpression plasmid, we transfected this plasmid and/or microRNA (miRNA)­196a mimic into ESCC cells (Eca109 cell line). Methyl thiazolyl tetrazolium (MTT) assay and Transwell chamber assay were performed to determine cell proliferation, migration and invasion, respectively. Western blot analysis was used to examine the protein expression levels of ANXA1, Snail and E-cadherin. RT-PCR was used to detect the expression of miRNA-196a. Our results revealed that ANXA1 expression was upregulated in the cells transfected with the ANXA1 overexpression plasmid, and cell proliferation, migration and invasion were significantly increased (p=0.004, p<0.001 and p=0.011, respectively). In the cells transfected with the miRNA­196a mimic, miRNA­196a expression was significantly upregulated (p<0.001). However, miRNA-196a expression was downregulated in the cells transfected with the ANXA1 overexpression plasmid. In addition, in the cells transfected with the miRNA­196a mimic, cell proliferation, migration and invasion were significantly decreased (p=0.027, p=0.009 and p=0.021, respectively). In the cells transfected with the ANXA1 overexpression plasmid, the expression of Snail was upregulated and that of E-cadherin was downregulated. However, the opposite was observed in the cells transfected with the miRNA­196a mimic. Our findings thus demonstrate that ANXA1 promotes the proliferation of Eca109 cells, and increases the expression of Snail, whereas it inhibits that of E-cadherin, thus enhancing the migration and invasion of ESCC cells. miRNA-196a negatively regulates the expression of ANXA1, thereby inhibiting the proliferation, invasion and metastasis of ESCC cells.

In vitro and in vivo antitumor evaluation of berbamine for lung cancer treatment.

PURPOSE: Lung cancer, one of the most frequently diagnosed cancers in the world, is characterized by relatively high morbidity and mortality. Berbamine (BER) has been initially reported to exert anti-proliferative effects against a series of cancers. METHODS: In this study the in vitro cytotoxicity of BER was measured by MTT assay. In vivo anti-cancer efficacy of BER was assessed in A549 xenografts. RESULTS: Cytotoxicity tests showed dose-dependent cell growth inhibition effects of BER against A549 cells. Moreover, BER significantly reduced the growth of lung cancer in a dose-dependent manner in nude mice with prolonged survival time. CONCLUSION: Therefore, BER might be in herbal medicine for cancer therapy and further efforts are needed to explore therapeutic strategies.