The interaction between miR148a and DNMT1 suppresses cell migration and invasion by reactivating tumor suppressor genes in pancreatic cancer.
Oncol Rep
; 40(5): 2916-2925, 2018 Nov.
Article
in En
| MEDLINE
| ID: mdl-30226601
ABSTRACT
DNA methylation is an epigenetic mechanism that cells use to control gene expression, which serves an important role in tumorigenesis. DNA methyltransferase 1 (DNMT1) is responsible for the maintenance of the pattern of DNA methylation. Overexpression of DNMT1 is observed in numerous malignant tumors, including pancreatic cancer, and results in silencing of several key tumor suppressor genes (TSGs). Recent studies have suggested that microRNAs (miRNAs/miRs) contribute to the regulation of DNMT1 expression, and promoter hypermethylation caused by DNMT1 overexpression is associated with the dysfunction of some miRNAs. The present study aimed to reveal the interaction between miR148a and DNMT1, and its effects on cell proliferation, migration and invasion of pancreatic cancer cells. Initially, the expression levels of DNMT1 and miR148a were detected in pancreatic cancer tissues and AsPC1 cells by reverse transcriptionquantitative polymerase chain reaction (PCR). Secondly, the regulatory effects of DNMT1 on miR148a were evaluated using methylationspecific PCR. Furthermore, bioinformatics analysis and dual luciferase reporter assay were used to verify the target relationship between miR148a and DNMT1. Finally, in vitro rescue experiments were conducted to evaluate the effects of miR148a on the expression of TSGs and the malignant phenotype in AsPC1 cells. The results demonstrated that DNMT1 was aberrantly upregulated in pancreatic cancer, and was responsible for hypermethylation of the miR148a promoter. Furthermore, DNMT1 was revealed as a direct target of miR148a by dual luciferase reporter assay, and restoration of miR148a could reactivate TSGs, such as p16, preproenkephalin and Ras association domain family member 1 by targeting DNMT1 in the AsPC1 pancreatic cancer cell line. These results indicated that an interaction exists between miR148a and DNMT1 in pancreatic cancer. Notably, miR148a overexpression significantly inhibited cell proliferation, migration and invasion in AsPC1 cells. Therefore, miR148a may serve as a novel therapeutic target for the treatment of pancreatic cancer.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
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DNA Methylation
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MicroRNAs
/
DNA (Cytosine-5-)-Methyltransferase 1
Limits:
Female
/
Humans
/
Male
Language:
En
Journal:
Oncol Rep
Journal subject:
NEOPLASIAS
Year:
2018
Document type:
Article