S100A10 promotes proliferation and invasion of lung adenocarcinoma cells by activating the Akt-mTOR signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effects of expression levels of S100 calcium-binding protein A10 (S100A10) in lung adenocarcinoma (LUAD) on patient prognosis and the regulatory role of S100A10 in lung cancer cell proliferation and metastasis.@*METHODS@#Immunohistochemistry was used to detect the expression levels of S100A10 in LUAD and adjacent tissues, and the relationship between S100A10 expression and clinicopathological parameters and prognosis of the patients was statistically analyzed. The lung adenocarcinoma expression dataset in TCGA database was analyzed using gene enrichment analysis (GSEA) to predict the possible regulatory pathways of S100A10 in the development of lung adenocarcinoma. Lactate production and glucose consumption of lung cancer cells with S100A10 knockdown or overexpression were analyzed to assess the level of glycolysis. Western blotting, CCK-8 assay, EdU-594 assay, and Transwell assays were performed to determine the expression level of S100A10 protein, proliferation and invasion ability of lung cancer cells. A549 cells with S100A10 knockdown and H1299 cells with S100A10 overexpression were injected subcutaneously in nude mice, and tumor growth was observed.@*RESULTS@#The expression level of S100A10 was significantly upregulated in LUAD tissues as compared with the adjacent tissues, and an elevated S100A10 expression level was associated with lymph node metastasis, advanced tumor stage and distant organ metastasis (P < 0.05), but not with tumor differentiation or the patients' age or gender (P > 0.05). Survival analysis showed that elevated S100A10 expressions in the tumor tissue was associated with a poor outcome of the patients (P < 0.001). In the lung cancer cells, S100A10 overexpression significantly promoted cell proliferation and invasion in vitro (P < 0.001). GSEA showed that the gene sets of glucose metabolism, glycolysis and mTOR signaling pathway were significantly enriched in high expressions of S100A10. In the tumor-bearing nude mice, S100A10 overexpression significantly promoted tumor growth, while S100A10 knockdown obviously suppressed tumor cell proliferation (P < 0.001).@*CONCLUSION@#S100A10 overexpression promotes glycolysis by activating the Akt-mTOR signaling pathway to promote proliferation and invasion of lung adenocarcinoma cells.

Analysis of filaggrin 2 gene polymorphisms in patients with atopic dermatitis

Abstract Background: Polymorphisms of the filaggrin 2 gene (rs 12568784 and rs 16899374) are associated with persistent atopic dermatitis in African American patients. Filaggrin 2 is a protein with a function similar to filaggrin and also encoded in the epidermal differentiation complex on chromosome 1q21. Objective: To evaluate the polymorphisms in the filaggrin 2 gene (rs 12568784 and rs 16899374) in children and adults with atopic dermatitis and to verify the association of these with the severity of the clinical picture, presence of other allergic diseases, and socio-demographic factors. Method: The study was carried out with patients and control group. Questionnaires were used to evaluate ethnicity, sex, age, family history, scoring, atopic dermatitis (SCORAD), among other parameters. Genotyping of the filaggrin 2 gene was performed by real-time polymerase chain reaction. Results: Forty-eight patients and 83 controls were evaluated. No correlation was found between the variables studied in patients with atopic dermatitis and polymorphisms, no significant difference between the prevalence of polymorphisms in the patients and in the control group p > 0.05. Study limits: The exclusive use of self-reported ethnicity information and the sample size. Results: The results of this work can be an incentive for the study of the polymorphisms in atopic dermaititis, considering the characteristic of the Brazilian multi ethnic population. Conclusion: This is an unpublished work in Brazil and the first study in the world to have a control group to evaluate alterations in the gene of filaggrin 2.

Growth and Invasion of Sporadic Colorectal Adenocarcinomas in Terms of Genetic Change

Integrative genetic changes were examined in relation to tumor growth and progression of sporadic colorectal cancers. Ninety-two sporadic colorectal cancer patients and 12 human colorectal cancer cell lines were evaluated. Genetic changes in representative steps of colorectal tumorigenesis were determined. Biological characteristics, i.e., clinicopathologic parameters, expression of invasion-associated molecules, and in vitro invasion and migration, in association with these changes were further analyzed. Adenomatous polyposis coli (APC) and/or Wnt-activated alterations occurred in 66% patients, whereas mismatch repair (MMR) defects and/or RAF-mediated alterations were identified in 47% patients. The crossover rate between these two alterations was 26%. Differential mRNA expression of ARK5 was closely associated with that of MMP2, MMP9, and S100A4 (P< or =0.044-0.001). Additionally, enhanced ARK5 mRNA expression was more frequent in tumors displaying RAF-mediated alterations and crossover pathways (P=0.01 and 0.03, respectively). Upregulation of CEA mRNA was more common in the advanced stages (P=0.034), while VEGF expression was greater in poorly differentiated or mucinous tumors (P=0.042). The high expressions of MMP2 and MMP9 were closely associated with invasion and migration of colorectal tumors and cell lines. Our results conclusively show that specific pathways of colorectal tumorigenesis are closely associated with characteristic tumor growth and invasion.