The epigenetic silencing of microRNA-433 facilitates the malignant phenotypes of non-small cell lung cancer by targeting CREB1

microRNA-433 的表观遗传沉默通过靶向 CREB1 促进非小细胞肺癌的恶性表型

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作者:Weige Wang, Chao Feng, Wenqiang Zhang, Yong Long, Xian'en Fa

Conclusion

We found that DNA methylation can downregulate miR-433 in NSCLC, which promotes the malignant behaviors of NSCLC cells.

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.

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.

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.

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