BMI-1, a polycomb ring finger oncogene, is highly expressed in multiple cancer cells and is involved in cancer cell proliferation, invasion, and apoptosis. BMI-1 represents a cancer stemness marker that is associated with the regulation of stem cell self-renewal. In this study, pharmacological inhibition (PTC596) or knockdown (siRNA) of BMI-1 reduced cancer stem-like cells and enhanced cancer cell death. Mechanistically, the inhibition of BMI-1 induced the downregulation of Mcl-1 protein, but not Mcl-1 mRNA. PTC596 downregulated Mcl-1 protein expression at the post-translational level through the proteasome-ubiquitin system. PTC596 and BMI-1 siRNA induced downregulation of DUB3 deubiquitinase, which was strongly linked to Mcl-1 destabilization. Furthermore, overexpression of Mcl-1 or DUB3 inhibited apoptosis by PTC596. Taken together, our findings reveal that the inhibition of BMI-1 induces Mcl-1 destabilization through downregulation of DUB3, resulting in the induction of cancer cell death.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472307 | PMC |
| http://dx.doi.org/10.3390/ijms221810107 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Resveratrol Can Differentiate Human Melanoma Stem-like Cells from Spheroids Treated With All-trans Retinoic Acid.
Anticancer Res
December 2024
Institute of Life Innovation Studies, Toyo University, Tokyo, Japan
Background/aim: Stem-like cancer cells are believed to be the leading cause of therapy resistance in malignant melanoma (MM). All-trans retinoic acid (ATRA) differentiation therapy is considered a promising approach to eradicate stem-like cancer cells, but some melanoma cells are resistant to ATRA. This study aimed to examine whether resveratrol (RS), a natural polyphenol compound, could improve the response of MM stem-like cells to ATRA and explore the possible underlying mechanisms.
View Article and Find Full Text PDFBmi-1 alleviates alveolar bone resorption through the regulation of autophagy.
J Periodontol
September 2024
Department of Stomatology, Children's Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Background: B-cell‑specific Moloney MLV insertion site-1(Bmi-1)is a crucial osteopenic target molecule. The aim of this study is to explore the effects of Bmi-1 on alveolar bone resorption and the underlying mechanisms in vitro and vivo.
Methods: A Bmi-1-knockout (Bmi-1) mouse model was used to investigate the effect of Bmi-1 on alveolar bone metabolism, with micro-computed tomography imaging, histology, and immunohistochemistry staining.
Bmi-1 Epigenetically Orchestrates Osteogenic and Adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells to Delay Bone Aging.
Adv Sci (Weinh)
December 2024
Department of Human Anatomy, Research Centre for Bone and Stem Cells, School of Basic Medical Sciences, Key Laboratory for Aging & Disease, School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
With the increase in the aging population, senile osteoporosis (SOP) has become a major global public health concern. Here, it is found that Prx1 and Bmi-1 co-localized in trabecular bone, bone marrow cavity, endosteum, and periosteum. Prx1-driven Bmi-1 knockout in bone-marrow mesenchymal stem cells (BMSCs) reduced bone mass and increased bone marrow adiposity by inhibiting osteoblastic bone formation, promoting osteoclastic bone resorption, downregulating the proliferation and osteogenic differentiation of BMSCs, and upregulating the adipogenic differentiation of BMSCs.
View Article and Find Full Text PDFBmi-1 promotes the proliferation, migration and invasion, and inhibits cell apoptosis of human retinoblastoma cells via RKIP.
Sci Rep
June 2024
Department of Ophthalmology, The Second People's Hospital of Jinan, No. 148, Jingyi Road, Jinan, 250000, Shandong, China.
Article Synopsis
- * Bmi-1 was found to enhance cell growth, migration, and invasion in retinoblastoma cells while reducing cell death; contrastingly, low levels of Bmi-1 and higher levels of RKIP showed the opposite effect.
- * Targeting Bmi-1 presents a promising therapeutic approach for retinoblastoma, with the Bmi-1/RKIP interaction being crucial in the cancer's progression.
Mechanisms of Hypercoagulability Driving Stroke Risk in Obesity: A Mendelian Randomization Study.
Neurology
July 2024
From the Department of Neurology (I.D.), University of California, San Francisco; and Department of Epidemiology and Biostatistics (D.G.), School of Public Health, Imperial College London, United Kingdom.
Background And Objectives: Obesity is hypothesized to induce a hypercoagulable state that increases stroke risk. The molecular mechanisms underlying this association are largely uncharacterized. We aimed to apply mendelian randomization to identify whether the association of genetically proxied body mass index (BMI) with cardioembolic stroke risk is mediated by changes in levels of circulating coagulation factors.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!