Similar Datasets
Project description:SETD1A catalyzes methylation of histone 3 lysine 4 (H3K4) and plays a critical role in development of multiple cancers. The abrrent expression of SETD1A relates to poor prognosis of gastric cancer (GC) patients. Here, we revealed that SETD1A is required for GC cell proliferation. Rescue experiment showed catalytic function is not necessary for GC cell growth and gene expression, whereas a novel non-catalytic FLOS domain is indispensable. The CRISPR screening targeting SETD1A targets identified that TAF6 acts as a downstream target of SETD1A which is essential for GC cell survival. Both SETD1A and TAF6 are required for G1/S cell cycle progression in GC cells. Non-catalytic component of SETD1A regulating expression of TAF6 through coactivating with E2F4s. These results demonstrate that non-canonical roles of SETD1A in GC cell, which supplys a potential therapeutic opportunity for GC.
2025-07-25 | GSE273825 | GEO
Project description:SETD1A catalyzes methylation of histone 3 lysine 4 (H3K4) and plays a critical role in development of multiple cancers. The abrrent expression of SETD1A relates to poor prognosis of gastric cancer (GC) patients. Here, we revealed that SETD1A is required for GC cell proliferation. Rescue experiment showed catalytic function is not necessary for GC cell growth and gene expression, whereas a novel non-catalytic FLOS domain is indispensable. The CRISPR screening targeting SETD1A targets identified that TAF6 acts as a downstream target of SETD1A which is essential for GC cell survival. Both SETD1A and TAF6 are required for G1/S cell cycle progression in GC cells. Non-catalytic component of SETD1A regulating expression of TAF6 through coactivating with E2F4s. These results demonstrate that non-canonical roles of SETD1A in GC cell, which supplys a potential therapeutic opportunity for GC.
2025-07-25 | GSE273824 | GEO
Project description:Non-catalytic role of SETD1A promotes gastric cancer cell proliferation through the E2F4-TAF6 axis in the cell cycle
| PRJNA1143411 | ENA
Project description:Non-catalytic role of SETD1A promotes gastric cancer cell proliferation through the E2F4-TAF6 axis in the cell cycle (ChIP-seq)
| PRJNA1143421 | ENA
Project description:Gastric cancer (GC) is a major health burden worldwide, but our understanding of GC is limited, and the prognosis is poor. Novel therapeutic strategies and biomarkers are urgently needed to improve GC patient outcomes. Previously, we identified PFDN2 as a novel key gene in gastric cancer based on its differential expression between cancer and normal tissues. However, the role and underlying mechanisms of PFDN2 in GC remain elusive. In this article, we demonstrated that PFDN2 is highly expressed in GC and that upregulation of PFDN2 is associated with the progression of GC. We further found that PFDN2 could promote cell cycle progression by promoting MYBL2 expression. Mechanistically, we demonstrated that PFDN2 could upregulate MYBL2 expression by facilitating the nuclear translocation of hnRNPD, and thus promoting MYBL2 transcriptional program. In conclusion, we found that PFDN2 promotes cell cycle progression via the hnRNPD-MYBL2 axis and may serve as a potential biomarker and therapeutic target for GC.
| S-EPMC10395514 | biostudies-literature
Project description:Gastric cancer (GC) is a malignancy for which effective therapeutic drugs are limited. Podofilox exhibits antitumor effects in various types of cancer; however, whether it may inhibit GC growth remains unknown. The aim of the present study was to investigate the role of podofilox in GC. Cell Counting Kit-8, colony formation and cell cycle assays were used to detect the role of podofilox on cellular proliferation and the cell cycle, respectively. A microarray was used to detect the transcriptional changes induced by podofilox in GC cells. The results of the present study demonstrated that podofilox inhibited GC cell proliferation and colony formation. The half maximal inhibitory concentration of podofilox in AGS and HGC-27 cells was 2.327 and 1.981 nM, respectively. In addition, treatment with podofilox induced G0/G1 cell cycle arrest. Molecular analysis based on microarray data demonstrated that podofilox altered the expression levels of genes involved in the cell cycle, c-Myc and p53 signaling. Autophagy-related 10 (ATG10), which was highly expressed in GC tissues, was also downregulated by podofilox, as demonstrated by the results of the microarray analysis and immunoblotting. To determine the involvement of ATG10 in GC, ATG10 was knocked down in GC cells by small interfering RNA, which suppressed the proliferation and colony formation of GC cells compared with those observed in the control-transfected cells. Taken together, the results of the present study suggested that podofilox may inhibit GC cell proliferation by preventing the cell cycle progression and regulating the c-Myc/ATG10 signaling pathway.
| S-EPMC8422391 | biostudies-literature
Project description:Background: The important role of nucleobindin 2 (NUCB2) in various cancers has been recently recognized. However, its biological functions and regulatory mechanisms in hepatocellular carcinoma (HCC) remain unclear. Methods: The expression level of NUCB2 in HCC was assessed using public databases, immunohistochemistry, and Western blotting. The effects of NUCB2 on cell proliferation and metastasis were investigated using colony formation, EdU, Transwell assays, and an in vivo mouse xenograft model. Regulation of E2F4 by NUCB2 was identified by protein half-life and in vivo ubiquitylation assays. The relationship between E2F4 and prostaglandin reductase 1 (PTGR1) was investigated by qRT-PCR, RT-PCR, and chromatin immunoprecipitation assays. Results: This study found that NUCB2 expression was significantly higher in HCC tissues than in normal liver tissues, and patients with high expression displayed shorter survival rates. Inhibition of NUCB2 reduced the proliferation and metastatic potential of HCC cells in vitro and in vivo. NUCB2 depletion reduced PTGR1 expression, which reduced cell proliferation and migration. Our findings suggested that NUCB2 suppressed E2F4 degradation by interacting with E2F4. Additionally, increased E2F4 levels facilitated PTGR1 transcription by directly binding to the PTGR1 promoter. Conclusion: This study demonstrated the oncogenic properties of NUCB2 in HCC and suggested that NUCB2 facilitates hepatocellular carcinoma progression by activating the E2F4/PTGR1 axis.
| S-EPMC11414389 | biostudies-literature
Project description:RNA polymerase II subunit A (POLR2A) is the largest subunit encoding RNA polymerase II and closely related to cancer progression. However, the biological role and underlying molecular mechanism of POLR2A in gastric cancer (GC) are still unclear. Our study demonstrated that POLR2A was highly expressed in GC tissue and promoted the proliferation of GC in vitro and in vivo. We also found that POLR2A participated in the transcriptional regulation of cyclins and cyclin-dependent kinases (CDKs) at each stage and promoted their expression, indicated POLR2A's overall promotion of cell cycle progression. Moreover, POLR2A inhibited GC cell apoptosis and promoted GC cell migration. Our results indicate that POLR2A play an oncogene role in GC, which may be an important factor involved in the occurrence and development of GC.
| S-EPMC8655910 | biostudies-literature
Project description:Androgen deprivation therapy eventually leads to the development of castration-resistant prostate cancer (CRPC). Here, we demonstrate for the first time that the histone H3K4 methyltransferase SETD1A is a major regulator for the proliferation of metastatic CRPC (mCRPC). The expression of SETD1A was significantly correlated with the survival rate of patients with prostate cancer. SETD1A, which is expressed at a higher level in mCRPC than in primary prostate cancer cells, promotes the expression of FOXM1, a gene encoding a cell proliferation-specific transcription factor. SETD1A is recruited to the promoter region of FOXM1 (forkhead box M1) upon binding to E2F1, a protein that regulates the transcription of FOXM1 and contributes to the trimethylation of H3K4 in the FOXM1 promoter region. In addition, SETD1A is essential for the expression of stem cell factor (e.g., OCT4, octamer-binding transcription factor 4) and stem cell formation in mCRPC, suggesting the importance of SETD1A expression in mCRPC tumor formation. Notably, poor prognosis is associated with high expression of the SETD1A-FOXM1 pair in clinical data sets. Therefore, our study suggests that SETD1A plays an important role in the proliferation of mCRPC by regulating FOXM1 transcription.
| S-EPMC7407996 | biostudies-literature
Project description:Circular RNAs are an important kind of noncoding RNAs and involved in cancerogenesis, but the specific mechanism between gastric cancer and circRNAs needs further study. Hsa_circ_0007967 was selected by RNA sequencing. Here, hsa_circ_0007967 was highly expressed in gastric cancer tissues than adjacent normal tissues. Overexpressing hsa_circ_0007967 promoted gastric cancer cell proliferation in vitro and in vivo, while suppression of hsa_circ_0007967 inhibited gastric cancer cell proliferation in vitro and in vivo. Mechanistically, hsa_circ_0007967 sponged miR-411-5p to increase MAML3 expression. Overall, hsa_circ_0007967 is a promising biomarker for gastric cancer diagnosis and a potential molecule for gastric cancer treatment.
| S-EPMC8969178 | biostudies-literature