Cancerous inhibitor of PP2A (protein phosphatase 2A) (CIP2A) is an inhibitor of PP2A, a phosphatase and tumor suppressor that regulates cell proliferation, differentiation, and survival. The aim of this study was to investigate whether CIP2A plays a role in the progression of myelodysplastic syndromes (MDS). Immunohistochemical analysis revealed that a fraction patients having refractory anemia with excess blasts (RAEB)-1 (4 out of 12) and RAEB-2 (10 out of 14) exhibited significant expression of CIP2A in bone marrow hematopoietic cells, while all patients with refractory cytopenia with unilineage or multilineage dysplasia (RCUD/RCMD) (0 out of 18) and the control group (0 out of 17) were negative. CIP2A was mainly expressed by the MPO-positive myeloid series of cells and partly by the CD34-positive cells in association with the expression of phosphorylated c-MYC (p-c-MYC) protein and the cell cycle-related proteins Ki-67, MCM2, and geminin. The percentage of p-c-MYC-positive cells in the bone marrow of CIP2A-positive MDS cases was significantly higher than that in CIP2A-negative MDS cases (P < 0.01). The expression levels of mRNA for CIP2A and PP2A exhibited positive correlation in MDS/control bone marrow. These results suggest that up-regulated expression of CIP2A might play a role in the proliferation of blasts in the MDS bone marrow and in disease progression in at least some cases.
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http://dx.doi.org/10.1007/s12253-013-9709-y | DOI Listing |
Nat Chem Biol
January 2025
Fudan University Shanghai Cancer Center, Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Shanghai Key Laboratory of Medical Epigenetics, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Chromatin and transcription regulators are critical to defining cell identity through shaping epigenetic and transcriptional landscapes, with their misregulation being closely linked to oncogenesis. Pharmacologically targeting these regulators, particularly the transcription-activating BET proteins, has emerged as a promising approach in cancer therapy, yet intrinsic or acquired resistance frequently occurs, with poorly understood mechanisms. Here, using genome-wide CRISPR screens, we find that BET inhibitor efficacy in mediating transcriptional silencing and growth inhibition depends on the auxiliary/arm/tail module of the Integrator-PP2A complex (INTAC), a global regulator of RNA polymerase II pause-release dynamics.
View Article and Find Full Text PDFJ Neurochem
January 2025
Department of Pathophysiology, School of Basic Medicine, Key Laboratory of Education Ministry/Hubei Province of China for Neurological Disorders, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Brain damage induced by ischemia promotes the development of cognitive dysfunction, thus increasing the risk of dementia such as Alzheimer's disease (AD). Studies indicate that cellular acidification-triggered activation of asparagine endopeptidase (AEP) plays a key role in ischemic brain injury, through multiple molecular pathways, including cleavage of its substrates such as SET (inhibitor 2 of PP2A, I ) and Tau. However, whether direct targeting AEP can effectively prevent post-stroke cognitive impairment (PSCI) remains unanswered.
View Article and Find Full Text PDFCancer Chemother Pharmacol
December 2024
Department of Orthopedics & Soft Tissue, The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University/Hunan Cancer Hospital, No. 283, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan Province, People's Republic of China.
Background: Polygala tenuifolia and its active components have been revealed to possess anti-tumor activities. However, the role of Tenuigenin (TEN), a bioactive ingredient from Polygala tenuifolia, in tumors such as osteosarcoma (OS) remains unclear. The present research intended to explore the efficacy and underlying mechanism of TEN on OS.
View Article and Find Full Text PDFComput Biol Med
December 2024
Biomedical Engineering Institute, Chiang Mai University, Chiang Mai, 50200, Thailand; Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand. Electronic address:
Jiaogulan (Gynostemma pentaphyllum) is a traditional herb with potential antidiabetic properties. This study investigated the underlying mechanisms of these properties by analysing plasma protein profiles in type 2 diabetes patients. A total of 42 participants were divided into three groups, each comprising 14 individuals: healthy controls (N), untreated type 2 diabetes patients (DM), and Jiaogulan-treated type 2 diabetes patients (DMJ).
View Article and Find Full Text PDFEur J Pharmacol
February 2025
Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan. Electronic address:
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