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Background and purpose: Gastric cancer is one of the common gastrointestinal malignancies. FKBP1A has been reported to be involved in the occurrence and development of various tumors, but the biological role and mechanism of it in gastric cancer remain unclear. This study aimed to investigate the expression level and prognostic value of FKBP1A in gastric cancer tissues, and to analyze the possible pathways and mechanisms of its regulation of gastric cancer progression. Methods: The expression of FKBP1A in gastric cancer was observed by immunohistochemistry, and its correlation with poor prognosis was analyzed by combining bioinformatics and clinicopathological parameters. Kaplan-Meier survival curve was used to analyze the effect of FKBP1A on the 5-year survival rate of patients with gastric cancer after surgery, and COX multivariate regression analysis was used to explore the independent prognostic factors affecting the 5-year survival rate of patients with gastric cancer after surgery. The diagnostic value of FKBP1A expression in patients with gastric cancer was analyzed using receiver operating characteristic (ROC) curve. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to enrich and analyze the biological function of FKBP1A and the possible signal pathways involved. We constructed the MGC803 cell model transfected with lentivirus in vitro, explored the influence of FKBP1A on the glucose metabolism and malignant biological behavior of MGC803 cells, and the possible molecular mechanism involved, and established a nude mouse transplantation tumor model in vitro to verify it. Results: Immunohistochemical results showed that FKBP1A was highly expressed in gastric cancer (P＜0.01), and bioinformatics and clinical parameter analysis showed that FKBP1A was associated with poor prognosis. Kaplan-Meier survival analysis and COX regression analysis showed that the expression level of FKBP1A was negatively correlated with 5-year survival. And carcinoembryonic antigen (CEA)≥5 μg/L, carbohydrate antigen (CA) 19-9≥37 kU/L, T stage (T3-T4) and N stage (N2-N3) were independent prognostic factors affecting the 5-year survival rate of gastric cancer patients after surgery (P＜0.05). ROC analysis showed that high expression of FKBP1A had good prognostic value (P<0.01). Enrichment of GO and KEGG suggested that FKBP1A was involved in regulating glucose metabolism in gastric cancer cells. In vitro experiments showed that overexpression of FKBP1A promoted glucose metabolism and proliferation, invasion and migration of MGC803 cells, while silencing of FKBP1A did the opposite (P＜0.05). In vivo experiments showed that overexpression of FKBP1A in gastric cancer cells promoted the growth of transplanted tumor in nude mice, while silencing FKBP1A inhibited it (P＜0.05). Mechanism analysis showed that overexpression of FKBP1A upregulated the expressions of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in gastric cancer cells, while silencing FKBP1A downregulated the expressions (P＜0.05). Conclusion: FKBP1A is highly expressed in gastric cancer tissues, and is associated with poor prognosis, which may be due to the promotion of glucose metabolism and malignant biological behavior of gastric cancer cells by activating PI3K/AKT. [ABSTRACT FROM AUTHOR]

Background and purpose: The novel centrosomal regulatory protein Sec23 homolog B (SEC23B) regulates autophagy in cells, thereby providing energy and nutrients that contribute to tumor growth and distant metastasis. However, whether this role is involved in the mechanism of infiltrative metastasis in breast cancer is unclear. The aim of this study was to investigate the molecular mechanism by which SEC23B promotes breast cancer infiltration and metastasis. Methods: The association between SEC23B expression and breast cancer prognosis and metastasis was analyzed using Kaplan-Meier Plotter database and HCMDB database. MCF-7 cells were divided into vector group (control) and SEC23B overexpression plasmid group (SEC23B), and MDA231-LM2 cells were divided into SEC23B knockdown group (sh-SEC23B) and control group (sh-NC). Western blot was used to detect the expressions of SEC23B, autophagy-associated proteins [dead bone fragment 1 (SQSTM1, p62), microtubule-associated-protein light-chain-3 (LC3)] and extracellular-regulated protein kinases (ERK)/mammalian target of rapamycin (mTOR) pathway proteins in breast cancer cells. Cell migration was assessed by transwell assay and wound healing assay, and autophagic granules in cells were detected by immunofluorescence staining. In addition, an in vivo intraperitoneal tumor model was constructed to study the effect of SEC23B on breast cancer cell metastasis in vivo. Results: The overall survival of breast cancer patients with high SEC23B expression was significantly shorter than that of patients with low SEC23B expression. The expression of SEC23B in metastatic breast cancer was significantly higher than that in breast cancer without metastasis. SEC23B protein levels were lower in primary breast cancer cells (MCF-7, BT-549, MDA-MB-468 and MDA-MB-453) than in metastatic breast cancer cells (MDA231- LM2 and ZR-75-30). Compared with the control group, the SEC23B group significantly accelerated cell migration (P<0.001). Compared with the sh-NC group, the sh-SEC23B group significantly reduced cell migration (P<0.001). Compared with the control group, the expression level of LC3A/B and the formation of autophagy particles in the SEC23B group were significantly increased, while the expression of p62 protein and the phosphorylation levels of mTOR and ERK were decreased. Compared with the sh-NC group, the LC3A/B expression level and the formation of autophagy particles were significantly decreased in the sh-SEC23B group, and the phosphorylation levels of mTOR and ERK were increased, especially under starvation conditions. In in vivo experiments, tumor weight was significantly lower in the sh-SEC23B group compared with the sh-NC group (P<0.01), and there was an increase in necrotic tissue and a decrease in tumor metastasis in lung tissue in mice. sh-SEC23B group mice had a significantly lower number of lung metastatic tumors and LC3 immunohistochemical staining than the sh-NC group (P<0.01). Conclusions: SEC23B induces breast cancer autophagy and promotes cancer cell metastasis by inhibiting ERK/mTOR signaling pathway. [ABSTRACT FROM AUTHOR]

Background and purpose: Breast cancer is the most common malignancy in women, and it is also the cancer with the highest number of new cases worldwide in 2020. Human epidermal growth factor receptor 2 (HER2)-positive breast cancer accounts for approximately 20% of all breast cancers, which indicates higher rate of recurrence and metastasis and a poor prognosis. Therefore, it is of great significance to explore the biomarkers related to HER2-positive breast cancer. This study aimed to investigate the expression of circ-0003910 in HER2-positive breast cancer tissues and cells, and to clarify the effect of circ-0003910 on the migration and invasion of breast cancer cells. Methods: Circular RNA (circRNA) microarray was used to screen circRNA differentially expressed in HER2-positive breast cancer cells, and significantly overexpressed circRNA was selected as the research target. Fluorescence in situ hybridization (FISH) assay was used to detect the subcellular localization of circ-0003910. BaseScope assay was used to analyze the expression and clinical significance of circ-0003910 in breast cancer tissues. Circ-0003910 overexpressed and knockdown breast cancer cells were constructed by transfection of cloned plasmid and siRNA in vitro. The effect of circ-0003910 on the migration and invasion ability of breast cancer cells was detected by transwell assay. The molecular mechanism of circ0003910 promoting the migration and invasion of breast cancer cells was preliminarily explored by TMT quantitative proteomics techniques. Results: CircRNA microarray analysis showed that a total of 1 843 differentially expressed circRNAs were screened in HER2-positive breast cancer cells (fold change≥2, P<0.05), including 845 upregulated circRNAs and 998 downregulated circRNAs. Compared with normal breast epithelial cells, the differential expression ratio of circ-0003910 in HER2-positive breast cancer cells was 24.39. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) results showed that the expression of circ0003910 was higher in HER2-positive breast cancer cells than in other molecular types of breast cancer cells, and BaseScope assay verified that circ-0003910 was mainly located in the cytoplasm of HER2-positive breast cancer tissue cells. Overexpression of circ0003910 promoted the migration and invasion of breast cancer cells, while circ-0003910 knockdown produced the opposite effects. Proteomics identification showed that 197 proteins were changed after overexpression of circ-0003910, of which 104 proteins were upregulated and 93 proteins were downregulated. GO and KEGG enrichment analysis suggested that circ-0003910 may be involved in biological processes such as cell adhesion molecule synthesis, transcriptional dysregulation in cancer, and protein digestion and absorption. Conclusion: Circ-0003910 is upregulated in breast cancer cells and can promote the migration and invasion of breast cancer cells, which may be a new biomarker and target for the treatment of metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Breast cancer is a malignant tumor with the highest incidence in women in the world, and it represents the leading cause of cancer-related deaths in women. Breast cancer is a highly heterogeneous disease, including the heterogeneity between tumors and even within the tumor microenvironment, making precise classification and treatment of the disease difficult. The application of traditional high-throughput sequencing technology in breast cancer research has provided an important reference for revealing the occurrence and development of breast cancer, driving genes, precise classification, diagnosis and treatment. However, the limitation of traditional high-throughput sequencing technology is its inability to explore heterogeneity within the tumor microenvironment. The single-cell sequencing technology emerged in recent years has been greatly improved in terms of sensitivity, accuracy and efficiency, enabling us to analyze single-cell genome information in complex mixed cells, which has shown great performance in studying tumor heterogeneity. In recent years, there are a number of important research results obtained by harnessing single-cell sequencing technology in breast cancer research, including analyzing breast cancer transcriptome at the single-cell level, exploring the heterogeneity of breast cancer microenvironment, breast cancer drug resistance mechanisms, the clonal heterogeneity and clonal evolution of breast cancer, and comprehensively mining single-cell public data resources to reveal the heterogeneity of breast cancer. This article reviewed important research in recent years regarding the application of single-cell sequencing technology in breast cancer era. We aimed to provide references for breast cancer researchers to manipulate the single-cell sequencing technology and promote the in-depth use of single-cell sequencing technology in breast cancer research. [ABSTRACT FROM AUTHOR]

Bone metastasis is one of the most serious complications in advanced breast cancer patients. Severe osteodynia, pathological fracture and other complications in bone metastasis of breast cancer can seriously affect the quality of life and shorten life span. In recent years, with the further understanding of the mechanism of bone metastases and the cross-talk between tumor cells and bone microenvironment, development and application of many new effective drugs have made significant progress in the treatment of bone metastasis of breast cancer. This article reviewed the mechanism of bone metastasis of breast cancer and current treatment advances. [ABSTRACT FROM AUTHOR]

Background and objective Bufalin, a component of the Chinese medicine chan'su, induces apoptosis in various human tumor cell lines. The aim of this study is to investigate the mechanism of anti-proliferation and the induction of apoptosis of Bufalin on non-small cell lung cancer cell. Methods The effect of Bufalin on A549 cell proliferation was measured using MTT assay; the morphological change was observed with Wright-Giemsa stain; cell cycle phase distribution and hypodiploid DNA were determined by flow cytometry with PI; expressions of Livin, Caspase-3 were detected by Western blot. Results MTT assay showed that Bufalin inhibited A549 cell proliferation in time and dose-dependent manner. The inhibition concentration of 50% cell growth (IC50) at 48 h, 72 h and 96 h were (56.14±6.72) nmol/L, (15.57±4.28) nmol/L and (7.39±4.16) nmol/L, respectively; apoptosis of A549 cells could be effectively induced by Bufalin; apoptotic bodies and sub-G1 peak (representing apoptosis) emerged when cells were treated with different concentrations, compared with the untreated control group (P<0.01). The expression of Livin protein was downregulated (P<0.01) and Caspase-3 protein was activated during Bufalin-induced apoptosis in A549 cells. Conclusion Bufalin suppresses the growth of A549 cells and induces apoptosis; inhibition of Livin and activation of Caspase-3 may be involved in its mechanism. [ABSTRACT FROM AUTHOR]

Background and objective It has been proven that MTA2 was expressed in many tumor cell lines and was correlated with tumor invasion and metastasis. The aim of this study is to investigate the expression of MTA2 protein in non-small cell lung cancer (NSCLC) and to explore the relationship between the expression of MTA2 and the pathological features. Methods The expression of MTA2 protein in 110 cases of NSCLC and 34 cases corresponding lung tissues was detected with immunohistochemistry method. The relationship between the expression of MTA2 and the pathological features in NSCLC was analyzed statistically. Results There was no expression of MTA2 protein in cancer collateral branch trachea epithelial and alveolar epithelial, but there was some expression in partial NSCLC. The positive rate of MTA2 was 58.18% (64/110) in 110 NSCLC cases. The expression of MTA2 had negative correlation with differentiation degree of NSCLC but had positive correlation with clinical stage and lymph node metastasis (P<0.05), moreover, it had no obvious correlation with age, gender and pathological type (P>0.05). Conclusion There was some expression of MTA2 in partial NSCLC and it was correlated with differentiation degree, clinical stage and lymph node metastasis. The results show that the occurrence and development of lung cancer may be related with MTA2. MTA2 may act as a new symbol and target in the treatment of lung cancer. [ABSTRACT FROM AUTHOR]