Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(12)
Published: Nov. 28, 2024
The mechanism for RNA methylation during disc degeneration is unclear. aim of this study was to identify N6-methyladenosine (m6A) markers and therapeutic targets the prevention treatment intervertebral (IDD).
Language: Английский
Molecular and Cellular Probes, Journal Year: 2025, Volume and Issue: unknown, P. 102024 - 102024
Published: March 1, 2025
Although great advances have been reached in the diagnosis, treatment and prognosis of kidney renal clear cell carcinoma (KIRC), advancement therapeutic strategies for KIRC clinical practices seriously limited due to its unknown molecular mechanisms. To resolve this issue, through analyzing datasets from online UCSC database, a novel BUB1 gene was found be elevated cancerous tissues compared their normal KIRC, patients with high-expressed tended worse prognosis. The subsequent experiments validated that protein located both nucleus cytoplasm cells, expression levels were significantly contrast counterparts. Loss-of-function verified knockdown suppressed proliferation, mobility, epithelial-mesenchymal transition (EMT) tumor growth, whereas induced apoptotic death cells vitro vivo. In addition, bioinformatics analysis predicted differentially-expressed genes (DEGs) BUB1-deficient cohorts enriched division-related PI3K/Akt signal pathway, we evidenced silencing capable inactivating downstream pathway. Of note, deficiency BUB1-induced suppressing effects on malignant phenotypes all reversed by co-treating pathway activator 740Y-P. Furthermore, it status related epigenetic modifications, immune infiltration immunotherapy responses KIRC. Collectively, inhibited progression could potentially used as biomarkers diagnosis clinic.
Language: Английский
Citations
0
Aging Cell, Journal Year: 2025, Volume and Issue: unknown
Published: March 25, 2025
Intervertebral disk degeneration (IDD) is a common age-related degenerative disease of the spine that imposes substantial economic burden on both families and society. Despite advances in understanding mechanisms underlying IDD, effective therapeutic interventions for its treatment prevention remain elusive. Our previous study identified positive correlation between IDD severity bromodomain-containing protein 4 (BRD4) expression. However, multifaceted role BRD4 still not fully understood. This explored abnormal elevation expression nucleus pulposus (NP) tissues from patients with an rat model IDD. We found levels were positively correlated NP senescence extracellular matrix (ECM) degradation inversely ECM anabolism. These relationships further confirmed through assays measuring senescence-associated β-galactosidase activity, markers P21 P16, secretory phenotype indicators (IL-6, IL-8, MMP3, MMP13), as well metabolism such collagen II aggrecan. Mechanistically, aberrant was to upregulate MAP2K7, which turn enhances PGF expression, promoting cell metabolism. findings highlight crucial BRD4/MAP2K7/PGF signaling axis cellular regulation, suggesting represents promising target
Language: Английский
Citations
0
Arthritis Research & Therapy, Journal Year: 2025, Volume and Issue: 27(1)
Published: April 17, 2025
Recently, several studies have reported that nucleus pulposus (NP) cell ferroptosis plays a key role in IDD. However, the characteristics and molecular mechanisms of subsets involved remain unclear. We aimed to define factors driving ferroptosis, ferroptotic NP cells during The accumulation iron ions tissues rats caudal intervertebral discs (IVDs) was determined by Prussian blue staining. Fluorescent probe Undecanoyl Boron Dipyrromethene (C11-BODIPY) lipid peroxidation product 4-Hydroxynonenal (4-HNE) staining were performed assess level cells. differentially expressed genes with aging overlapped FerrDB database screen associated aging-related In addition, single sequencing (ScRNA-seq) used map cells, further identify subsets, as well their crucial drivers. Finally, cluster analysis marker Histological showed that, compared 10 months old (10M-old) group, increased 20 (20M-old) rats, also enhanced. 15 related IDD selected cross-enrichment. ScRNA-seq identified 14 tissue among which number ratio 5 reduced, intracellular signaling pathways significantly enriched, accompanied enhanced peroxidation. Notably, ranking up-regulation fold genes, we found Atf3 always present within TOP2 these five suggests it is factor ferroptosis. cross-enrichment fluorescence colocalization revealed Rps6 +/Cxcl1- common feature subsets. This study reveals ATF3 driver IDD, These findings provide evidence theoretical support for subsequent targeted intervention directions preventing delaying
Language: Английский
Citations
0
The Journals of Gerontology Series A, Journal Year: 2024, Volume and Issue: 79(8)
Published: June 10, 2024
Abstract Background Nucleus pulposus cell (NPC) senescence in intervertebral disc (IVD) tissue is the major pathological cause of degeneration (IDD). N6-methyladenosine (m6A) methylation and gut microbiota play important roles progression IDD. This study investigated whether methyltransferase-like 3 (METTL3) regulates TLR2 m6A modification to influence NPC senescence. Methods An IDD rat model was established by lumbar IVD puncture NPCs were challenged with IL-1β mimic injury. rats IL-1β-exposed treated METTL3-interfering lentivirus agonist Pam3CSK4. Compositional changes analyzed fecal transplantation procedures used. senescence, cycle, expression senescence-associated secretory phenotype (SASP) factors assessed. The enrichment binding IGF2BP1 mRNA examined. Results METTL3 highly expressed rats. silencing attenuated senescent phenotypes reduced secretion SASP factors. Pam3CSK4 reversed beneficial effects on stabilized an IGF2BP1-dependent manner. restored specific levels rats, which further administration Fecal from silenced altered Conclusions These results demonstrate amelioration injury, involving modulation microbiota. findings support as a potential therapeutic target for
Language: Английский
Citations
3
International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8335 - 8335
Published: July 30, 2024
Cell transplantation is being actively explored as a regenerative therapy for discogenic back pain. This study the potential of Tie2
Language: Английский
Citations
1
Frontiers in Bioscience-Landmark, Journal Year: 2024, Volume and Issue: 29(12)
Published: Nov. 28, 2024
The mechanism for RNA methylation during disc degeneration is unclear. aim of this study was to identify N6-methyladenosine (m6A) markers and therapeutic targets the prevention treatment intervertebral (IDD).
Language: Английский
Citations
0