Orc2 siRNA_Lentivectors
- Known as:
- Orc2 siRNA_Lentivectors
- Catalog number:
- i065258a
- Product Quantity:
- 500ng
- Category:
- -
- Supplier:
- ABM
- Gene target:
- Orc2 siRNA_Lentivectors
Related genes to: Orc2 siRNA_Lentivectors
- Gene:
- ORC2 NIH gene
- Name:
- origin recognition complex subunit 2
- Previous symbol:
- ORC2L
- Synonyms:
- -
- Chromosome:
- 2q33.1
- Locus Type:
- gene with protein product
- Date approved:
- 1995-09-28
- Date modifiied:
- 2016-10-05
Related products to: Orc2 siRNA_Lentivectors
Related articles to: Orc2 siRNA_Lentivectors
- Pressure injuries develop when prolonged compression of the skin and subcutaneous tissue impairs blood circulation, leading to localized tissue ischemia, degeneration, and ultimately necrosis. Ischemia-reperfusion(I/R) injury is one of the key pathological mechanisms underlying pressure injury formation. While cellular senescence has been implicated in I/R-related pathologies, its role in pressure injury development remains unclear. We aimed to elucidate the mechanisms of keratinocyte senescence in cutaneous I/R injury. An in vitro hypoxia/reoxygenation (H/R) model was employed to simulate I/R injury using human immortalized keratinocytes (HaCaT). H/R induction significantly exacerbated the senescence response, as characterized by reduced cell proliferation, increased apoptosis, elevated SA-β-galactosidase (SA-β-gal) activity, and upregulated expression of senescence markers (p16 and p21). Quantitative proteomic analysis identified CDC6 as a prominently upregulated protein under H/R conditions. siRNA-mediated CDC6 knockdown attenuated keratinocyte senescence, restored G1/S phase cyclin-D1 (CCND1) expression, and suppressed p53 levels, demonstrating its regulatory role in senescence via the p53/CCND1 pathway. Furthermore, protein interaction network analysis and experimental validation revealed CDC6's direct binding with origin recognition complex 2 (ORC2), evidenced by nuclear colocalization (immunofluorescence) and physical interaction (co-immunoprecipitation). Collectively, our findings pioneers the mechanistic elucidation of CDC6 in pressure injury pathology, proposing senescence-targeted interventions as a novel therapeutic strategy for ulcer management. - Source: PubMed
Publication date: 2026/01/22
Wang ChenmingZhu ShanshanDai MeigeChen Hui - Within the framework of discovering novel colorectal cancer chemotherapeutic agents with improved efficacy and safety profiles, efforts were directed towards advancing this area of research. In this study, new pyrazolo[3,4-b]pyridine series were designed as Cyclin Dependent Kinase 2 (CDK2) inhibitors, synthesized, and biologically evaluated. All chemical structures were docked into the active site of CDK2 crystalline structure (1HCK). Binding energies and receptor interactions were elucidated. Antiproliferative activities against human colorectal cancer (CRC) cell lines HCT-116, HT-29 and related cytotoxicity on non-tumorigenic human colorectal cell line NCM-460D were studied by MTT assays. Compounds 6, 9c, 10, and 14 possessed notable activity against HCT-116 and HT-29 cells with IC values ranging from 11.11 to 62.61 μM. Compounds 6, 10, and 14 exhibited low cytotoxicity on NCM-460D, promoting them as promising chemotherapeutic agents. Structure-Activity Relationship of synthesized compounds was established, highlighting the influence of extended planarity, aromatic environments, and presence of electron donor-acceptor groups. Compounds 6 and 14 were selected for molecular investigations. They were not considered pro-apoptotic and showed non-significant influence on CDK2 protein expression. However, they displayed a dose-dependent inhibition of CDK2 kinase activity in in-vitro ADP-Glo™ assay with IC values of 23.47 and 82.04 nM, respectively, compared to 0.51 and 700 nM for Dinaciclib and Roscovitine, respectively. Compound 6 downregulated CDK2 protein targets involved in DNA replication process; Polα, MCM7, ORC2, and ORC4 in CRC cell lines. Subjected to cell cycle analysis, HCT-116 and HT-29 treated with compound 6 demonstrated pre-G1 phase arrest with no similar observation in S phase. - Source: PubMed
Publication date: 2025/12/03
Issa Doaa A EKassem Zahra AStaiteieh Soumaiah AbouYoussef AliNasr JamalDarwiche NadineMerhi Raghida Abou - Precision therapy for glioma remains a major challenge due to tumor heterogeneity. The Origin Recognition Complex Subunit 6 (ORC6) is a crucial regulator of DNA replication initiation. This study aims to investigate the expression of ORC6 in gliomas and its relationship with survival rates and malignancy, while screening potential drugs targeting its functional network. By integrating multiple bioinformatics approaches with structure-based virtual screening, retrospective RNA sequencing data analysis was performed using patients from the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) databases. A protein-protein interaction (PPI) network was constructed from ORC6-coexpressed genes to identify core hubs. Molecular docking was employed to screen a library of natural compounds and known drugs against these hub targets. Research has revealed that ORC6 is significantly upregulated in high-grade gliomas, with its elevated expression associated with poor survival outcomes and immune inflammatory responses. Network analysis identified five core hub genes (ORC1, ORC2, MCM2, MCM6, CDC45) central to DNA replication. Molecular docking revealed that several compounds, including the natural flavonoid Baicalein and the FDA-approved drug Palbociclib, exhibited high binding affinity to these hub targets. ORC6 represents a highly promising novel target for precision therapy in glioma. Potential approaches to target this pathway include disrupting the ORC6-replication axis using existing drugs (such as palbociclib) or natural products (such as baicalin). - Source: PubMed
Publication date: 2025/11/19
Wang MengjieFeng SongZhang ChenJin Feng - - Source: PubMed
Publication date: 2025/10/16
Su ZhangliTian MengxueShibata EtsukoShibata YoshiyukiYang TianyiWang ZhenjiaJin FulaiZang ChongzhiDutta Anindya - Replication stress is a major driver of genomic instability and a hallmark of cancer cells. Although dynamic heterochromatin remodeling has been implicated in replication stress response, the precise mechanisms remain unclear. Here, we identify the CHAMP1 complex, composed of CHAMP1, POGZ, HP1α, and the H3K9 methyltransferase SETDB1, as a critical regulator of heterochromatin assembly at stalled replication forks. Upon replication stress, the CHAMP1 complex is recruited to stalled forks where it facilitates H3K9me3 deposition, creating a repressive chromatin environment that shields replication forks from MRE11-mediated degradation. The complex promotes the recruitment of the origin recognition complex (ORC) to sites of replication stress, such as the telomeric heterochromatin in alternative lengthening of telomeres (ALT)-positive tumor cells, thereby supporting efficient telomeric DNA replication. Loss of CHAMP1 disrupts ORC2 recruitment and impairs fork restart, leading to increased micronuclei formation and heightened sensitivity to replication stress. Notably, CHAMP1 deficiency induces synthetic lethality with FANCM inhibition in ALT-positive tumor cells, and the CHAMP1 complex is essential for the survival of CCNE1-amplified ovarian cancers. These findings uncover a chromatin-based mechanism of replication fork stabilization and suggest that CHAMP1 may represent a candidate therapeutic vulnerability in cancers with elevated replication stress. - Source: PubMed
Publication date: 2025/08/05
Li FengElbakry AmiraZhou Felix YZhang TianpengRavindranathan RamyaNguyen HuySyed AleemSun LifangMukkavalli SirishaGreenberg Roger AD'Andrea Alan D