Gastric cancer (GC) is a malignancy of the digestive tract with rapid progress, poor prognosis, and low survival rate. The aberrant expression of microRNA (miRNA) is closely related to the tumorigenesis and progression of GC. The purpose of this study was to investigate the effects of miR-137 on the proliferation, apoptosis, and migration of GC cells. Bioinformatics analysis revealed that EZH2 expression in GC based on The Cancer Genome Atlas (TCGA) dataset was dramatically increased, miR-137 expression was down-regulated, and miR-137 was remarkably negatively correlated with EZH2 in GC. Next, it was found that EZH2 expression was significantly increasing and miR-137 was significantly decreasing by quantitative polymerase chain reaction (qRT-PCR) in GC clinical specimens. In addition, miR-137 expression in GC cell lines was significantly lower than that in normal gastric parietal cells. TargetScan and star-Base were employed to predict that EZH2 was a potential target of miR-137, and subsequent luciferase reports confirmed this prediction. Western blot assay demonstrated that up-regulation of miR-137 decreased EZH2 expression in BGC-823 cells, whereas silenced miR-137 enhanced EZH2 expression in SGC-7901 cells. The gain/loss-of-function indicates that miR-137 regulates the proliferation, apoptosis, migration and epithelial-mesenchymal transition of GC cells. In conclusion, our findings indicate that miR-137 restrains migration and proliferation and induces apoptosis partially through negatively regulating the expression of EZH2 in GC cells.
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http://dx.doi.org/10.1615/CritRevEukaryotGeneExpr.2022041013 | DOI Listing |
Sci Rep
January 2025
Department of Spinal Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, China.
Inflammation aggravates secondary damage following spinal cord injury (SCI). M1 microglia induce inflammation and exert neurotoxic effects, whereas M2 microglia exert anti-inflammatory and neuroprotective effects. The sine oculis homeobox (SIX) gene family consists of six members, including sine oculis homeobox homolog 1 (SIX1)-SIX6.
View Article and Find Full Text PDFTher Adv Med Oncol
January 2025
Department of Molecular Biology of Cancer, Medical University of Lodz, Mazowiecka 6/8, Lodz 92-215, Poland.
The enhancer of zeste homolog 2 (EZH2) is a catalytic component of Polycomb repressive complex 2 (PRC2) mediating the methylation of histone 3 lysine 27 (H3K27me3) and hence the epigenetic repression of target genes, known as canonical function. Growing evidence indicates that EZH2 has non-canonical roles that are exerted as PRC2-dependent and PRC2-independent methylation of non-histone proteins, and methyltransferase-independent interactions of EZH2 with various proteins contributing to gene expression regulation and alterations in the protein stability. is frequently mutated and/or its expression is deregulated in various cancer types.
View Article and Find Full Text PDFLeukemia
January 2025
Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore.
The polycomb protein EZH2 is up-regulated in Chronic Myeloid Leukaemia (CML) and associated with transcriptional reprogramming. Here we tested whether EZH2 might also act as a modulator of the mRNA splicing landscape to elicit its oncogenic function in CML. We treated CML cell lines with EZH2 inhibitors and detected differential splicing of several hundreds of events, potentially caused by the transcriptional regulation of splicing factors.
View Article and Find Full Text PDFExp Hematol Oncol
January 2025
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Background: Osimertinib has emerged as a critical element in the treatment landscape following recent clinical trials. Further investigation into the mechanisms driving resistance to Osimertinib is necessary to address the restricted treatment options and survival advantages that are compromised by resistance in patients with EGFR-mutated lung adenocarcinoma (LUAD).
Methods: Spatial transcriptomic and proteomic analyses were utilized to investigate the mechanisms of Osimertinib resistance.
Molecules
December 2024
Department of Experimental Medicine, Sapienza University of Rome, 00161 Rome, Italy.
Enhancer of zeste homolog 2 (EZH2) is a methyltransferase involved in cell cycle regulation, cell differentiation, and cell death and plays a role in modulating the immune response. Although it mainly functions by catalyzing the tri-methylation of H3 histone on K27 (H3K27), to inhibit the transcription of target genes, EZH2 can directly methylate several transcription factors or form complexes with them, regulating their functions. EZH2 expression/activity is often dysregulated in cancer, contributing to carcinogenesis and immune escape, thereby representing an important target in anti-cancer therapy.
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