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The impacts of ubiquilin 1 (UBQLN1) knockdown on cells viability, proliferation, and apoptosis are mediated by p53 in A549 lung cancer cells
- Source :
- J Thorac Dis
- Publication Year :
- 2020
- Publisher :
- AME Publishing Company, 2020.
-
Abstract
- Background Little is known about the relationship between ubiquilin 1 (UBQLN1) and p53, both of them have been implicated in the development and progression of non-small cell lung cancer (NSCLC). In this study, we aimed to explore the role of loss of UBQLN1 in cell viability and proliferation, and cell apoptosis in human lung adenocarcinoma A549 cells. Methods Cell viability, proliferation, and apoptosis were determined by MTT, BrdU, and TUNEL assays, respectively. Adenoviruses carrying cDNA or siRNA were used to overexpress or silence target protein. Dihydroethidium (DHE) staining was performed to measure the real-time formation of intracellular reactive oxygen species (ROS). The chymotrypsin-like activity of 20S proteasome core was determined by using synthetic fluorogenic peptide substrate. Results UBQLN1 silencing led to a reduction of p53 protein levels and overexpression of p53 reversed the effects of UBQLN1 knockdown (KD) on cell viability, proliferation, and apoptosis. Furthermore, deficiency of UBQLN1 activated autophagy activity but did not affect proteasome activity. Inhibition of autophagy restored p53 protein levels in UBQLN1-KD A549 cells. In addition, UBQLN1 KD markedly inhibited phosphorylation of mammalian target of rapamycin (mTOR) and its downstream ribosomal S6 kinase (S6K). Conclusions Our experiments suggested that the regulation of UBQLN1 on cell viability, proliferation, and apoptosis was mediated by mTOR/autophagy/p53 signaling pathway.
- Subjects :
- 0301 basic medicine
Pulmonary and Respiratory Medicine
A549 cell
Gene knockdown
biology
business.industry
Autophagy
P70-S6 Kinase 1
Cell biology
Ribosomal s6 kinase
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
Apoptosis
030220 oncology & carcinogenesis
biology.protein
Medicine
Original Article
Viability assay
business
PI3K/AKT/mTOR pathway
Subjects
Details
- ISSN :
- 20776624 and 20721439
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Journal of Thoracic Disease
- Accession number :
- edsair.doi.dedup.....cc4016e43b0993e3e5a403658814653b