ABSTRACT
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.
Subject(s)
Humans , MicroRNAs/genetics , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/radiotherapy , Lung Neoplasms/genetics , Lung Neoplasms/radiotherapy , Gene Expression Regulation, Neoplastic , Cell Movement , Cell Line, Tumor , Epithelial-Mesenchymal TransitionABSTRACT
@# Objective: To screen differentially expressed lncRNA, miRNA and mRNA in colorectal cancer (CRC) in TCGA database, and to explore their relationship with CRC prognosis and related biological functions. Methods: RNA sequencing (RNA-Seq) data and miRNA-Seq data of CRC samples were downloaded from the TCGAdatabase and analyzed, and differentially expressed lncRNA, miRNA and mRNA were screened by R program. The lncRNA-miRNA-mRNA ceRNA network in CRC was constructed by analyzing and integrating the relationships between differentially expressed RNAs through miRcode, TargetScan and miRTarbase databases.KaplanMeier method was used to analyze the relationship between the expression of lncRNA, miRNA, mRNA in ceRNA network and the survival prognosis of patients.Finally, the signal pathways involved in the occurrence and development of CRC were analyzed by GSEA functional enrichment analysis software. Results: A total of 614 differentially expressed lncRNAs, 244 differentially expressed miRNAs, and 12 672 differentially expressed mRNAs in CRC were identified; a ceRNA network consisting of 139 lncRNAs, 37 miRNAs and 228 mRNAs was constructed;It was found that 58 lncRNAs, 23 miRNAs, and 150 mRNAs were associated with the prognosis of CRC.The results of GSEA enrichment analysis showed that mRNA was mainly involved in signaling pathways such as Notch, Hedgehog and TGF-β. Conclusion: CRC-related ceRNA network was successfully constructed and lncRNAs, miRNAs and mRNAs associated with CRC prognosis were screened. It provides a valuable preliminary basis for further in-depth clinical research and basic experimental research on CRC.