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

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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.

Medienart:

Artikel

Erscheinungsjahr:

2021

Erschienen:

2021

Enthalten in:

Zur Gesamtaufnahme - volume:13

Enthalten in:

American journal of translational research - 13(2021), 11 vom: 22., Seite 12302-12317

Sprache:

Englisch

Beteiligte Personen:

Wang, Weige [VerfasserIn]
Feng, Chao [VerfasserIn]
Zhang, Wenqiang [VerfasserIn]
Long, Yong [VerfasserIn]
Fa, Xian'en [VerfasserIn]

Themen:

C-phosphate-G island
Cyclic-AMP responsive element binding protein 1
DNA methylation
Journal Article
MicroRNA-433
Non-small cell lung cancer
Promoter region

Anmerkungen:

Date Revised 28.12.2021

published: Electronic-eCollection

Citation Status PubMed-not-MEDLINE

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM334923433