Weige Wang1, Chao Feng1, Wenqiang Zhang1, Yong Long1, Xian'en Fa2. 1. Department of Thoracic Surgery, The Second Affiliated Hospital of Zhengzhou University Zhengzhou 450014, He'nan Province, China. 2. Department of Cardiac Surgery, The Second Affiliated Hospital of Zhengzhou University Zhengzhou 450014, He'nan Province, China.
Abstract
OBJECTIVE: MicroRNAs (miRNAs) play a big role in the regulation of non-small cell lung cancer (NSCLC) development. The objective of this study is to determine how DNA methylation regulates miR-433 in NSCLC. METHODS: The degree of DNA methylation was determined, and the relevance of miR-433 and the features of NSCLC patients were assessed. The MiR-433 and CREB1 expressions were tested, and the biological characteristics of the NSCLC cells were determined. Subcutaneous tumorigenesis in nude mice and luciferase activity assays were performed. RESULTS: MiR-433 was downregulated, and CREB1 was upregulated in the NSCLC tissues, and the methylating rate of the C-phosphate-G (CpG) island in the miR-433 promoter region was enhanced. MiR-433 was also downregulated, and CREB1 was upregulated in the NSCLC cells and there was a low degree of promoter methylation of miR-433 in the NSCLC cells after demethylation. Upregulated miR-433 or downregulated CREB1 repressed the cell vitality and colony formation abilities and increased the amount of apoptotic A549 cells. Moreover, upregulated miR-433 also decelerated tumor growth. Conversely, the H460 cells and xenografts with reduced miR-433 or overexpressed CREB1 had contrary results. CREB1 was found to be targeted by miR-433, as verified by a luciferase activity assay. CONCLUSION: We found that DNA methylation can downregulate miR-433 in NSCLC, which promotes the malignant behaviors of NSCLC cells. AJTR
OBJECTIVE: MicroRNAs (miRNAs) play a big role in the regulation of non-small cell lung cancer (NSCLC) development. The objective of this study is to determine how DNA methylation regulates miR-433 in NSCLC. METHODS: The degree of DNA methylation was determined, and the relevance of miR-433 and the features of NSCLC patients were assessed. The MiR-433 and CREB1 expressions were tested, and the biological characteristics of the NSCLC cells were determined. Subcutaneous tumorigenesis in nude mice and luciferase activity assays were performed. RESULTS: MiR-433 was downregulated, and CREB1 was upregulated in the NSCLC tissues, and the methylating rate of the C-phosphate-G (CpG) island in the miR-433 promoter region was enhanced. MiR-433 was also downregulated, and CREB1 was upregulated in the NSCLC cells and there was a low degree of promoter methylation of miR-433 in the NSCLC cells after demethylation. Upregulated miR-433 or downregulated CREB1 repressed the cell vitality and colony formation abilities and increased the amount of apoptotic A549 cells. Moreover, upregulated miR-433 also decelerated tumor growth. Conversely, the H460 cells and xenografts with reduced miR-433 or overexpressed CREB1 had contrary results. CREB1 was found to be targeted by miR-433, as verified by a luciferase activity assay. CONCLUSION: We found that DNA methylation can downregulate miR-433 in NSCLC, which promotes the malignant behaviors of NSCLC cells. AJTR
Keywords:
C-phosphate-G island; DNA methylation; cyclic-AMP responsive element binding protein 1; microRNA-433; non-small cell lung cancer; promoter region
Authors: Zuzana Pastorkova; Jozef Skarda; Jozef Andel Journal: Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub Date: 2016-04-21 Impact factor: 1.245
Authors: X Xu; Y Zhu; Z Liang; S Li; X Xu; X Wang; J Wu; Z Hu; S Meng; B Liu; J Qin; L Xie; X Zheng Journal: Cell Death Dis Date: 2016-02-04 Impact factor: 8.469