miR-93-5p suppresses cellular senescence by directly targeting Bcl-w and p21

• Published in: Biochemical and biophysical research communications Vol. 505; no. 4; pp. 1134 - 1140
• Main Authors: Choi, Jae Yeon, Shin, Hyun Jin, Bae, In Hwa
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 10.11.2018
• Subjects: 60 APPLIED LIFE SCIENCES; Apoptosis Regulatory Proteins - antagonists & inhibitors; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Bcl-w; CARCINOMAS; CELL PROLIFERATION; Cellular senescence; Cellular Senescence - drug effects; Cyclin-Dependent Kinase Inhibitor p21 - antagonists & inhibitors; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Cyclin-Dependent Kinase Inhibitor p21 - metabolism; GALACTOSIDASE; GLIOMAS; HISTONES; Humans; INFLAMMATION; LUNGS; LYSINE; MicroRNAs - genetics; MicroRNAs - pharmacology; miR-93-5p; p21; Phenotype; Tumor Cells, Cultured; Bcl-w; miR-93-5p; p21; Cellular senescence
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.10.010

Cellular senescence, a distinctive type of irreversible growth arrest, develops in response to various stimuli. Bcl-w, an oncogene and member of the Bcl-2 family, has been reported to promote tumorigenicity in various cancer cells. Here, we sought to explore the potential role of Bcl-w in premature senescence, which has received relatively little research attention. Our findings demonstrate that Bcl-w enhances the activity of senescence-associated β-galactosidase (SA-β-gal) and promotes histone H3 tri-methylation at lysine 9 (H3K9me3) and expressions of p53, Notch2, p21, and p16—hallmarks of the senescent phenotype—in human U251 glioblastoma and H460 lung carcinoma cells. It is also known that microRNAs (miRNAs) regulate processes related to tumor development, such as cell proliferation, differentiation, survival, metabolism, inflammation, invasion, angiogenesis, and senescence. In this context, we found that miR-93-5p inhibited premature cellular senescence by directly suppressing Bcl-w and p21 expressions. Collectively, these findings suggest that targeting miR-93-5p–regulated Bcl-w may be a useful strategy for preventing premature senescence. •Overexpression of Bcl-w promoted activities of SA-ß-gal and H3K9me3.•Bcl-w induced expressions of senescence-related proteins.•In this study, we investigated the mechanism of Bcl-w-induced premature cellular senescence in GBM and lung cancer cells.