Nucleoporin 37 promotes the cell proliferation, migration, and invasion of gastric cancer through activating the PI3K/AKT/mTOR signaling pathway.

Gastric cancer is a kind of malignant tumor in the world. Emerging studies have proved the regulatory role of nucleoporin 37 in the development of several malignant tumors. However, the potential effect of NUP37 in gastric cancer is still unclear. In this study, we searched for the Cancer Genome Atlas analysis to explore the potential correlation between NUP37 and gastric cancer. Then, we analyzed NUP37 expression in gastric cancer tissues and cell lines. After constructing a NUP37-silenced model in NCI-N87 cells and a NUP37-overexpressed model in MKN45 cells, we evaluated the role of NUP37 in cell proliferation, migration, and invasion as well as its underlying mechanism. TCGA analysis showed that NUP37 expression was highly expressed in stomach adenocarcinoma, which showed a lower survival rate than normal samples. Moreover, NUP37 was found to be highly expressed in gastric cancer tissues and cell lines. Functionally, NUP37 deficiency promoted gastric cancer cell apoptosis and inhibited cell proliferation, migration, and invasion, whereas NUP37 overexpression exhibited the opposite results. Mechanically, upregulation of NUP37 activated the PI3K/AKT/mTOR signaling pathway. Furthermore, the rescue assay exhibited that the mTOR inhibitor rapamycin significantly reversed the promoting effect of NUP37 in cell proliferation, migration, and invasion. In conclusion, our study identified that NUP37 promoted malignant behavior of gastric cancer cells including invasion, proliferation, and migration through activating the PI3K and its downregulated signaling pathway, indicating that NUP37 might become a novel prognostic target for further gastric cancer therapy.

Knockdown of Serum- and Glucocorticoid-Regulated Kinase 1 Enhances Cisplatin Sensitivity of Gastric Cancer Through Suppressing the Nuclear Factor Kappa-B Signaling Pathway.

BACKGROUND: Previous studies have published the promoting effect of serum and glucocorticoid-regulated kinase 1 (SGK1) in various malignant tumors. However, whether SGK1 promotes gastric cancer remains a mystery. AIMS: To clarify the function of SGK1 in gastric cancer and its potential regulatory mechanism. STUDY DESIGN: Cell culture study. METHODS: The SGK1-silenced model was generated in two gastric cancer cell lines and further evaluated their malignant behavior and susceptibility to cisplatin. The interaction between miR-15a-5p and SGK1 was evaluated by the luciferase reporter assay. The knockdown efficiency of SGK1 was confirmed by RT- qPCR and Western blot assays. Cell proliferation rate was assessed with CCK-8 assay, and flow cytometry was used to determine cell cycle progression and apoptosis. RESULTS: Western blot data displayed an elevated level of SGK1 in gastric cancer cell lines. Functionally, SGK1 deficiency suppressed gastric cancer cell proliferation (P < .01) by acting on cell-cycle progression. Moreover, SGK1 deficiency suppressed cell invasion and migration of gastric cancer cells (P < .01). Further, the silencing of SGK1 obviously suppressed cell proliferation and induced apoptosis of the cells after cisplatin treatment (P < .01), indicating that SGK1 deficiency facilitated the chemosensitivity of these 2 gastric cancer cell lines to cisplatin. Mechanically, downregulation of SGK1 repressed the cytoplasm- to-nucleus translocation of NF-κB p65. Interestingly, we found that miR-15a-5p binds to the 3'UTR of SGK1, which was confirmed using luciferase activity assay (P < .05). Moreover, the data suggested that SGK1 reversed the suppression effect of miR-15a-5p on gastric cancer cell migration (P < .01). CONCLUSION: Loss of SGK1 suppresses the malignant behavior of gastric cancer cells and increases cisplatin sensitivity by restraining the NF-κB signaling pathway. Moreover, SGK1 may exert an inhibitory effect in gastric cancer by being targeted by miR-15a-5p. Therefore, SGK1 may be a prospective target for future gastric cancer therapy.

Binding of circulating anti-MUC1 antibody and serum MUC1 antigen in stage IV breast cancer.

The present study aimed to investigate the binding of circulating mucin 1 (MUC1) antibody with serum MUC1 antigen in stage IV breast cancer. Serum samples of 61 patients with stage IV breast cancer and 64 patients with early-stage breast cancer were collected. The anti­MUC1 antibody (IgG) and MUC1 antigen (cancer antigen 15­3; Ca15­3) were detected using an indirect enzyme-linked immunosorbent assay (I­ELISA) and ELISA, respectively. The MUC1 IgG affinity was detected using a urea degradation combining ELISA. Western blot analysis and an inhibition test were performed for verification of the binding of anti­MUC1 IgG with MUC1 antigen, and their correlation was analyzed. The results showed that there was a negative correlation between anti­MUC1 IgG and CA15­3 antigen in stage IV breast cancer when positive CA15­3 antigen and/or anti­MUC1 IgG were selected (r=­0.417; P=0.0044). The positive anti­MUC1 IgG with positive Ca15­3 antigen was more common in stage IV breast cancer, compared with early­stage breast cancer (χ2=4.629; P=0.031), however, Ca15­3 antigen positivity was higher in stage IV breast cancer, compared with early­stage breast cancer (χ2=10.58; P=0.001). Anti­MUC1 IgG was able to bind to the MUC1 antigen in stage IV breast cancer. No differences in the 8R-MUCPT inhibition ratio were found between the two groups (P=0.778), and there were no differences in the affinity of anti­MUC1 IgG (P=0.873). In stage IV breast cancer, circulating anti­MUC1 antibody was found to bind serum MUC1 antigen, although their compatibility was low. No significant difference was found in the affinity of the anti­MUC1 antibody between stage IV breast cancer and early­stage breast cancer.