miR-183 promotes radioresistance of lung adenocarcinoma H1299 cells via epithelial-mesenchymal transition

Lung adenocarcinomas are usually sensitive to radiation therapy, but some develop resistance. Radiation resistance can lead to poor patient prognosis. Studies have shown that lung adenocarcinoma cells (H1299 cells) can develop radioresistance through epithelial-mesenchymal transition (EMT), and this process is regulated by miRNAs. However, it is unclear which miRNAs are involved in the process of EMT. In our present study, we found that miR-183 expression was increased in a radioresistant lung adenocarcinoma cell line (H1299R cells). We then explored the regulatory mechanism of miR-183 and found that it may be involved in the regulation of zinc finger E-box-binding homeobox 1 (ZEB1) expression and mediate EMT in lung adenocarcinoma cells. qPCR results showed that miR-183, ZEB1, and vimentin were highly expressed in H1299R cells, whereas no difference was observed in E-cadherin expression. Western blot results showed that ZEB1 and vimentin were highly expressed in H1299R cells, while E-cadherin expression was decreased. When miR-183 expression was inhibited in H1299R cells, radiation resistance, proliferation, and cell migration were decreased. The expression of ZEB1 and vimentin in H1299R cells was decreased, while the expression of E-cadherin was increased. Moreover, miR-183 overexpression in H1299 cells enhanced radiation resistance, proliferative capacity, and cell migration ability. The expression of ZEB1 and vimentin in H1299 cells was increased, while that of E-cadherin was decreased. In conclusion, miR-183 may promote EMT and radioresistance in H1299 cells, and targeting the miR-183-ZEB1 signaling pathway may be a promising approach for lung cancer treatment.

Research on differentially expressed genes related to substance and energy metabolism between healthy volunteers and splenasthenic syndrome patients with chronic superficial gastritis / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To analyze the metabolic states of the lipids, protein, carbohydrate, and nucleic acid for chronic superficial gastritis patients of splenasthenic syndrome (SS), and to explore the pathogenesis mechanism of SS based on substance and energy metabolisms.</p><p><b>METHODS</b>During June 2004 to March 2005, recruited were four chronic superficial gastritis patients of SS who visited at the First Hospital of Guangzhou University of Chinese Medicine and Guangdong Provincial Hospital of Traditional Chinese Medicine. Four healthy volunteers were recruited from Guangzhou University of Chinese Medicine. Their gastric mucosa was extracted to perform experiments of DNA microarray. The dual-channel DNA microarray data were mined and bioinformatics analyzed by BRB ArrayTools and IPA software.</p><p><b>RESULTS</b>Fifteen genes were involved in substance and energy metabolisms in 20 differentially expressed genes, accounting for 75%.Among these genes, one gene was up-regulated, 14 genes down-regulated, and 11 genes were enzyme gene. Differentially expressed genes related to lipid metabolism included ACAA2 and CYP20A1, manifested as fatty acid catabolism and cholesterol transformation. Genes related to protein metabolism included ALDH9A1, ASL, ASS1, PCY-OX1L, RPS28, UBE2D2, UBXN1, B3GNT1, GCNT1, and PPP1R3C, manifested as decreased amino acid metabolism that may affect the biologic processes such as autonomic nerve, urea cycle, etc., reduced protein synthesis, increased ubiquitination of fault fold proteins, and decreased post-translated modification of glycosylation and dephosphorylation. Genes related to carbohydrate metabolism included PPP1R3C, B3GNT1, and GCNT1, manifested as decreased glycogen and glycan syntheses. Genes related to nucleic acid metabolism included RMI1, SMARCD3, and PARP1, manifested as degraded DNA duplication and transcription, and increased DNA damage repair.</p><p><b>CONCLUSIONS</b>The metabolisms of the lipids, protein, carbohydrate, and nucleic acid in chronic superficial gastritis patients of SS obviously decreased, manifested mainly as down-regulated enzyme gene expression. We inferred that these might be one of the vital pathogenesis mechanisms for nutrition dysmetabolism of SS.</p>