Downregulation of microRNA-27b-3p via aberrant DNA methylation contributes to malignant behavior of gastric cancer cells by targeting GSPT1

•MiR-27b-3p was downregulated in gastric cancer tissues and cells.•MiR-27b-3p can suppress gastric cancer cell proliferation, invasion, and migration.•MiR-27b-3p was downregulated by aberrant DNA methylation in gastric cancer.•GSPT1 was negatively regulated by miR-27b-3p via combining the 3′-untrans...

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Published in:Biomedicine & pharmacotherapy Vol. 119; p. 109417
Main Authors: Zhang, Cheng, Zou, Ying, Dai, Dong-Qiu
Format: Journal Article
Language:English
Published: France Elsevier Masson SAS 01.11.2019
Subjects:
Aberrant DNA methylation
Base Sequence
Cell Line, Tumor
Cell Movement - genetics
Cell Proliferation - genetics
DNA Methylation - genetics
Down-Regulation - genetics
Female
Gastric cancer
Gene Expression Regulation, Neoplastic
GSPT1
Humans
Male
MicroRNAs - genetics
MicroRNAs - metabolism
Middle Aged
miR-27b-3p
Neoplasm Invasiveness
Neoplasm Staging
Peptide Termination Factors - genetics
Peptide Termination Factors - metabolism
Promoter Regions, Genetic
Stomach Neoplasms - genetics
Stomach Neoplasms - pathology
Survival Analysis
miR-27b-3p
Aberrant DNA methylation
Gastric cancer
GSPT1
ISSN:0753-3322, 1950-6007, 1950-6007
Online Access:Get full text
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Summary:•MiR-27b-3p was downregulated in gastric cancer tissues and cells.•MiR-27b-3p can suppress gastric cancer cell proliferation, invasion, and migration.•MiR-27b-3p was downregulated by aberrant DNA methylation in gastric cancer.•GSPT1 was negatively regulated by miR-27b-3p via combining the 3′-untranslated region. Epigenetics play a vital role in the initiation and development of cancers, including gastric cancer (GC). In the present study, we aimed to explore potential up- and downstream mechanisms of miR-27b-3p in GC. The expression level of miR-27b-3p in GC cells and tissues (n = 80) was measured by quantitative RT-PCR. The mimics, inhibitors, and negative controls of miR-27b-3p were transfected into cell lines to perform the gain and loss of function study. Cell proliferation, migration, and invasion assays were utilized to assess biological behaviors caused by miR-27b-3p in vitro. Common target genes were predicted using four biological software programs and used for gene functional enrichment analysis. GSPT1 was selected for target gene verification using dual luciferase assays and its expression level was detected by western blot. The MKN-45 cell line was treated with 5-aza-2′-deoxycytidine (5-Aza-dC) and the methylation level was measured by methylation-specific PCR (MSP). miR-27b-3p was significantly downregulated in the GC cell lines and tissues compared with the normal group. The expression of miR-27b-3p was determined to be negatively associated with TNM stage and tumor size using statistical analysis. Overexpression of miR-27b-3p inhibited MKN-45 and SGC-7901 cell proliferation, invasion, and migration. Gene functional enrichment analysis indicated that the target genes were involved in several signaling pathways. Dual luciferase assays showed that miR-27b-3p combined with the 3′-untranslated region of GSPT1 mRNA. MSP demonstrated that miR-27b-3p promoter CpG island was hyper-methylated and 5-Aza-dC was able to partially reverse the methylation. Our study data indicated that miR-27b-3p is downregulated by aberrant DNA methylation in GC. In addition, miR-27b-3p suppresses GC cell proliferation, invasion, and migration via negative expression regulation of GSPT1, which could be a potential therapeutic target.
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ISSN:0753-3322
1950-6007
1950-6007
DOI:10.1016/j.biopha.2019.109417