Study on the mechanism of BGN in progression and metastasis of ccRCC
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1100931 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28704962_1.fastq.gz | Fastqsanger.gz | |||
| SRR28704962_2.fastq.gz | Fastqsanger.gz | |||
| SRR28704963_1.fastq.gz | Fastqsanger.gz | |||
| SRR28704963_2.fastq.gz | Fastqsanger.gz | |||
| SRR28704964_1.fastq.gz | Fastqsanger.gz |
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Project description:Based on multiple public databases, we investigated the expression level of BGN in ccRCC, its clinical significance, and its association with immune cells. Real-time fluorescence quantitative PCR was employed to validate BGN expression in tumor and adjacent normal tissues. Differential gene analysis, GO-KEGG analysis, and GSEA analysis were performed by RNA sequencing to elucidate the underlying signaling pathways. BGN knockdown cells were generated through lentiviral transfection to examine the impact of BGN on ccRCC. Cell proliferation, migration, and invasion were assessed using CCK8, colony formation, wound healing, Transwell migration, and invasion assays, respectively. Results: Our findings from database analysis and polymerase chain reaction (PCR) revealed a significant upregulation of BGN expression in kidney cancer tissues compared to normal tissues. Further analysis demonstrated a correlation between high BGN expression and ccRCC progression and immune infiltration. In vitro experiments confirmed that BGN silencing effectively inhibited cell proliferation, migration, and invasion of ccRCC. Mechanistically, these effects may be mediated through the MAPK signaling pathway. Conclusion: BGN potentially plays a pivotal role in the progression and metastasis of ccRCC, possibly acting through the MAPK signaling pathway. Therefore, BGN holds promise as a potential therapeutic target for ccRCC.
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Project description:Metastatic clear cell renal cell carcinoma (ccRCC) has a poor prognosis and unpredictable course and there are no molecular markers that reliably predict ccRCC metastasis. In this study, specimens from 84 patients with ccRCC were directly cultured in vitro. The primary cultures from 38 of 94 specimens contained more than 90% tumor cells at 4th passages. After identified by immunostaining, the primary cultures of metastatic- and nonmetastatic ccRCC specimens from the age-, gender-matched patients were subjected to cDNA microrray assays. A total of 842 differentially expressed genes with FDR (false discovery rate) = 4.79% were identified by using SAM (Significance Analysis of Microarray) software. Pathway enrichment and co-occurrence with “cancer”, “metastasis” and “invasion” in the literature annotations enriched the functions of the 842 genes and indicated the reliability of our microarray assays. Novel genes associated with metastasis were selected based on intra-molecular interaction between 205 differentially expressed genes co-occurred with “metastasis” and those not appeared with “metastasis” on Medline, as well as co-expression analysis between 205 differentially expressed genes co-occurred with “metastasis” and those not appeared on Medline in 12 microarray data. FSTL1, AV722783, SLC15A1, DDX17, ORC2L and PKMYT1 were proved to be potential ccRCC metastasis-associated novel genes, based on its expression patterns in the cultures and tumor tissues. Interestingly, the up-regulated genes (CAV1, PKMYT1 and ORC2L) were up-regulated and the down-regulated genes (FSTL1, GSTM3, CYR61, SLC15A1 and AV722783) were down-regulated, in the primary ccRCC specimens as compared with its adjacent normal kidney in 37 patients (determined by semi-quantitative RT-PCR). This study provides potential biomarkers and novel molecular targets for the early diagnosis and treatment of ccRCC metastasis. Keywords: Homo sapiens Because of limited cell number of primary cultures, total RNA of the primary cultures from 2 age and gender matched patients was pooled for each microarray assay. Each assay was technically repeated once. Cy3-labeled 1st cDNA synthesized from total RNA of the metastatic ccRCC pool was mixed with Cy5-labeled 1st cDNA synthesized from total RNA of the non-metastatic ccRCC pool, and hybridized to 16K cDNA chips (GEO Platform ID: GPL6259; SBC-R-HC-100-22, National Engineering Center for Biochip, Shanghai, China) that included 14784 unigenes, 241 negative controls and 527 positive controls. In our study we used a co-expression analysis for the relationship between genes; three gastric cancer Samples were only introduced to this analysis methods.
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Project description:DPF3, a component of the SWI/SNF chromatin remodeling complex, has been associated with clear cell renal cell carcinoma (ccRCC) in a genome-wide association study. However, the functional role of DPF3 in ccRCC development and progression remained unknown. In this study, we demonstrated that DPF3a, the short isoform of DPF3, could promote kidney cancer cell migration both in vitro and in vivo, consistent with the clinical observation that DPF3a was significantly upregulated in ccRCC patients with metastasis. Mechanistically, DPF3a specifically interacted with SNIP1, via which it formed a complex with SMAD4 and p300 histone acetyltransferase (HAT), the major transcriptional regulators of TGF-β signaling pathway. Moreover, the binding of DPF3a could release the repressive effect of SNIP1 on p300 HAT activity, leading to increased local histone acetylation and activation of cell movement related genes. In summary, our findings uncovered a novel link between chromatin remodeling and tumor metastasis, whose inhibition is a key therapeutic goal for ccRCC treatment.
2022-07-07 | GSE175845 | GEO
Project description:DPF3, a component of the SWI/SNF chromatin remodeling complex, has been associated with clear cell renal cell carcinoma (ccRCC) in a genome-wide association study. However, the functional role of DPF3 in ccRCC development and progression remained unknown. In this study, we demonstrated that DPF3a, the short isoform of DPF3, could promote kidney cancer cell migration both in vitro and in vivo, consistent with the clinical observation that DPF3a was significantly upregulated in ccRCC patients with metastasis. Mechanistically, DPF3a specifically interacted with SNIP1, via which it formed a complex with SMAD4 and p300 histone acetyltransferase (HAT), the major transcriptional regulators of TGF-β signaling pathway. Moreover, the binding of DPF3a could release the repressive effect of SNIP1 on p300 HAT activity, leading to increased local histone acetylation and activation of cell movement related genes. In summary, our findings uncovered a novel link between chromatin remodeling and tumor metastasis, whose inhibition is a key therapeutic goal for ccRCC treatment.
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Project description:Metastatic clear cell renal cell carcinoma (ccRCC) has a poor prognosis and unpredictable course and there are no molecular markers that reliably predict ccRCC metastasis. In this study, specimens from 84 patients with ccRCC were directly cultured in vitro. The primary cultures from 38 of 94 specimens contained more than 90% tumor cells at 4th passages. After identified by immunostaining, the primary cultures of metastatic- and nonmetastatic ccRCC specimens from the age-, gender-matched patients were subjected to cDNA microrray assays. A total of 842 differentially expressed genes with FDR (false discovery rate) = 4.79% were identified by using SAM (Significance Analysis of Microarray) software. Pathway enrichment and co-occurrence with “cancer”, “metastasis” and “invasion” in the literature annotations enriched the functions of the 842 genes and indicated the reliability of our microarray assays. Novel genes associated with metastasis were selected based on intra-molecular interaction between 205 differentially expressed genes co-occurred with “metastasis” and those not appeared with “metastasis” on Medline, as well as co-expression analysis between 205 differentially expressed genes co-occurred with “metastasis” and those not appeared on Medline in 12 microarray data. FSTL1, AV722783, SLC15A1, DDX17, ORC2L and PKMYT1 were proved to be potential ccRCC metastasis-associated novel genes, based on its expression patterns in the cultures and tumor tissues. Interestingly, the up-regulated genes (CAV1, PKMYT1 and ORC2L) were up-regulated and the down-regulated genes (FSTL1, GSTM3, CYR61, SLC15A1 and AV722783) were down-regulated, in the primary ccRCC specimens as compared with its adjacent normal kidney in 37 patients (determined by semi-quantitative RT-PCR). This study provides potential biomarkers and novel molecular targets for the early diagnosis and treatment of ccRCC metastasis. Keywords: Homo sapiens
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Project description:Renal cell carcinoma (RCC), the third most prevalent urological cancer, claims more than 100,000 lives/year worldwide. The clear cell (ccRCC) is the most common and aggressive subtype of renal cancer. Commonly asymptomatic, more than 30% of ccRCCs are diagnosed when they are already metastatic resulting in a 95% mortality rate and one-third of organ-confined cancers treated by nephrectomy develop metastasis during the follow-up. Diagnosis and monitoring requires expensive and frequent imaging examinations; thereby, finding of diagnostic and prognostic biomarkers to screen, diagnose and monitor renal cancers are clearly needed. Hepatitis A virus receptor/kidney injury molecule 1 (HAVCR1/KIM-1) gene has been claimed to be a susceptibility gene for ccRCC and HAVCR1/KIM-1 ectodomain shedding a predictive biomarker of tumor progression.
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