Bromodomain adjacent to zinc finger domain protein 1A (ATP-dependent chromatin-remodeling protein) (ATP-utilizing chromatin assembly and remodeling factor 1) (hACF1) (CHRAC subunit ACF1) (Williams syndrome transcription factor-related chromatin-remodeling factor 180) (WCRF180) (hWALp1) [ACF1] [WCRF180] [HSPC317]
развернуть
Chromatin remodeling factor
BAZ1A regulates cellular senescence in both cancer and normal cells.
Cellular senescence is a well-known cancer prevention mechanism, inducing cancer cells to senescence can enhance cancer immunotherapy. However, how cellular senescence is regulated is not fully understood. Dynamic chromatin changes have been discovered during cellular senescence, while the causality remains elusive. BAZ1A, a gene coding the accessory subunit of ATP-dependent chromatin remodeling complex, showed decreased expression in multiple cellular senescence models. We aim to investigate the functional role of BAZ1A in regulating senescence in cancer and normal cells. Knockdown of BAZ1A was performed via lentivirus mediated short hairpin RNA (shRNA) in various cancer cell lines (A549 and U2OS) and normal cells (HUVEC, NIH3T3 and MEF). A series of senescence-associated phenotypes were quantified by CCK-8 assay, SA-β-Gal staining and EdU incorporation assay, etc. KEY FINDINGS: Knockdown (KD) of BAZ1A induced series of senescence-associated phenotypes in both cancer and normal cells. BAZ1A-KD caused the upregulated expression of SMAD3, which in turn activated the transcription of p21 coding gene CDKN1A and resulted in senescence-associated phenotypes in human cancer cells (A549 and U2OS). Our results revealed chromatin remodeling modulator BAZ1A acting as a novel regulator of cellular senescence in both normal and cancer cells, indicating a new target for potential cancer treatment.
MeSH Terms
- A549 Cells
- Animals
- Bone Neoplasms
- Cells, Cultured
- Cellular Senescence
- Chromatin Assembly and Disassembly
- Chromosomal Proteins, Non-Histone
- Fibroblasts
- Human Umbilical Vein Endothelial Cells
- Humans
- Mice
- NIH 3T3 Cells
- Osteosarcoma
- Signal Transduction
- Transcription Factors
Keywords
- BAZ1A
- Chromatin remodeling factor
- SMAD3
- Senescence