KIAA1429 promotes cell proliferation by regulating MYC messenger RNA in clear cell renal cell carcinoma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1157345 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30552053_1.fastq.gz | Fastqsanger.gz | |||
| SRR30552053_2.fastq.gz | Fastqsanger.gz | |||
| SRR30552054_1.fastq.gz | Fastqsanger.gz | |||
| SRR30552054_2.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:KIAA1429 is an integral component of the m6A methyltransferase complex, essential for facilitating the interaction between the catalytic core components METTL3 and METTL14. However, the mechanisms by which KIAA1429 influences clear cell Renal cell carcinoma (ccRCC) remain incompletely elucidated. Analysis of the TCGA and GEO database confirmed that KIAA1429 was significantly upregulated in ccRCC samples, which correlated with poor survival. Additionally, qRT-PCR, Western Blot and IHC detection revealed significantly upregulated levels of KIAA1429 in ccRCC tissues. Moreover, multivariable Cox regression analysis showed that patients with ccRCC with high KIAA1429 expression had a poor clinical prognosis. Notably, silencing KIAA1429 significantly inhibited the proliferation, migration and invasion of ccRCC cells. Similarly, KIAA1429 knockdown also significantly inhibited the growth of ccRCC cells in nude mice. Mechanistically, KIAA1429 silencing significantly reduced the overall level of m6A in, the stability of MYC mRNA and the mRNA and protein expressions of MYC in ccRCC cells. Furthermore, RIP-qRT-PCR experiments showed that KIAA1429 could directly bind to MYC mRNA. MeRIP assay revealed that KIAA1429 knockdown resulted in a significant decrease in the m6A level of MYC mRNA in ccRCC cells. In conclusion, KIAA1429 regulates the proliferation, migration and invasion of ccRCC cells by stabilizing MYC mRNA in an m6A-dependent manner. Therefore, targeting the KIAA1429-MYC signalling pathway emerges as a potential strategy for the treatment of renal cell carcinoma.
2024-09-10 | GSE276431 | GEO
Project description:N6-methyladenosine (m6A) modification, as the most abundant internal methylation of eukaryotic RNA transcripts, is critically implicated in RNA processing, decay, transport and translation. Here we showed that KIAA1429, the largest known component in the m6A methyltransferase complex, was considerably upregulated in hepatocellular carcinoma (HCC) tissues. High expression of KIAA1429 was significantly associated with the malignant clinical features and the poor prognosis of HCC patients. Silencing KIAA1429 suppressed the cell proliferation and metastasis in vitro and in vivo. Integrated MeRIP-seq, RIP-seq and RNA-seq data identified GATA3 as the direct downstream target of KIAA1429-mediated m6A modification. KIAA1429 knockdown markedly impaired the m6A levels of GATA3 mRNA and increased the expression of GATA3. Mechanistically, KIAA1429 induced the m6A methylation on 3’ UTR of GATA3 pre-mRNA, leading to the separation of RNA-binding protein HuR and the degradation of GATA3 pre-mRNA, which was followed by the downregulation of GATA3. Strikingly, a long noncoding RNA (lncRNA) GATA3-AS, transcribed from the antisense strand of GATA3 gene, functioned as a cis-acting element for the preferential interaction of KIAA1429 with GATA3 pre-mRNA. Accordingly, we found that the tumor growth and metastasis driven by KIAA1429 or GATA3-AS were mediated by GATA3. Patients with low KIAA1429 and high GATA3 expressions showed greatly better poor overall survival and disease-free survival. In conclusion, our study proposed a complex KIAA1429-GATA3 regulatory model based on m6A modification and provided insights into the epi-transcriptomic dysregulation in hepatocarcinogenesis and metastasis.
2019-07-27 | GSE134978 | GEO
Project description:N6-methyladenosine (m6A) is the most abundant internal RNA modification in mRNA molecules and plays important roles in multiple important biological processes including cancer development. KIAA1429/VIRMA is an important component of m6A methyltransferase complex to facilitate depositing m6A modification in RNA molecules. Here we found that KIAA1429/VIRMA was overexpressed in breast cancer patients among other m6A related enzymes. Breast cancer patients with higher KIAA1429 expression have worse survival compared with control group. In addition, KIAA1429/VIRMA protein mislocated in cytosol in breast cancer tissues and cell lines. KIAA1429/VIRMA depletion reduced breast cancer cell proliferation and migration. Mechanism studies showed that cytosolic expressed KIAA1429/VIRMA interacted with m6A reader protein IGF2BP3 and stabilized expression of m6A-modified HAS2 expression. HAS2 is downstream of KIAA1429/VIRMA to mediate breast cancer cell proliferation and migration and has positive correlation with KIAA1429/VIRMA expression in cancer patients.
2021-11-02 | GSE185494 | GEO
Project description:Background: N6-Methyladenosine (m6A) methylation, a common form of RNA modification, play an important role in the pathogenesis of various diseases and in the ontogeny of organisms. Nevertheless, the precise function of m6A methylation in photoaging remains unknown. Objectives: This study aims to investigate the biological role and underlying mechanism of m6A methylation in photoaging. Methods: m6A dot blot, Real-time quantitative PCR (RT-qPCR), western blot and immunohistochemical (IHC) assays were employed to detect the m6A level and specific m6A methylase in ultraviolet ray (UVR)-induced photoaging tissue. The profile of m6A-tagged mRNA was identified by methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq analysis. Finally, we investigated the regulatory mechanism of KIAA1429 by MeRIP-qPCR, RNA knockdown and immunofluorescence assay. Results: m6A levels were increased in photoaging and were closely associated with the upregulation of KIAA1429 expression. 1331 differentially m6A methylated genes were identified in the UVR group compared with the control group, of which 1192 (90%) were hypermethylated. Gene ontology analysis showed that genes with m6A hypermethylation and mRNA downregulation were mainly involved in extracellular matrix metabolism and collagen metabolism-related processes. Furthermore, KIAA1429 knockdown abolished the downregulation of TGF-R and upregulation of MMP1 in UVR-irradiated HDFs. Mechanically, we identified MFAP4 as a target of KIAA1429-mediated m6A modification and KIAA1429 might suppress collagen synthesis through an m6A-MFAP4-mediated process. Conclusions: The increased expression of KIAA1429 hinders collagen synthesis during UVR-induced photoaging, suggesting that KIAA1429 represents a potential candidate for targeted therapy to mitigate UVR-driven photoaging.
2024-07-16 | GSE268348 | GEO
Project description:Clear cell renal cell carcinoma (ccRCC) is a common malignant tumor of the urogenital tract. Given that ccRCC is often resistant to radiotherapy and traditional chemotherapy, the clinical treatment of patients with ccRCC remains a challenge. The present study found that ATAD2 was significantly upregulated in ccRCC tissues. In vitro and in vivo experiments showed that the inhibition of ATAD2 expression mitigated the aggressive phenotype of ccRCC. ATAD2 was also associated with glycolysis in ccRCC. Interestingly, we found that ATAD2 could physically interact with c-Myc and promote the expression of its downstream target gene, thereby enhancing the Warburg effect of ccRCC. Overall, our study emphasizes the role of ATAD2 in ccRCC. The targeted expression or functional regulation of ATAD2 could be a promising method to reduce the proliferation and progression of ccRCC.
| S-EPMC10219916 | biostudies-literature
Project description:BackgroundTumor-infiltrating immune cells have been linked to prognosis and response to immunotherapy; however, the levels of distinct immune cell subsets and the signals that draw them into a tumor, such as the expression of antigen presenting machinery genes, remain poorly characterized. Here, we employ a gene expression-based computational method to profile the infiltration levels of 24 immune cell populations in 19 cancer types.ResultsWe compare cancer types using an immune infiltration score and a T cell infiltration score and find that clear cell renal cell carcinoma (ccRCC) is among the highest for both scores. Using immune infiltration profiles as well as transcriptomic and proteomic datasets, we characterize three groups of ccRCC tumors: T cell enriched, heterogeneously infiltrated, and non-infiltrated. We observe that the immunogenicity of ccRCC tumors cannot be explained by mutation load or neo-antigen load, but is highly correlated with MHC class I antigen presenting machinery expression (APM). We explore the prognostic value of distinct T cell subsets and show in two cohorts that Th17 cells and CD8+ T/Treg ratio are associated with improved survival, whereas Th2 cells and Tregs are associated with negative outcomes. Investigation of the association of immune infiltration patterns with the subclonal architecture of tumors shows that both APM and T cell levels are negatively associated with subclone number.ConclusionsOur analysis sheds light on the immune infiltration patterns of 19 human cancers and unravels mRNA signatures with prognostic utility and immunotherapeutic biomarker potential in ccRCC.
| S-EPMC5114739 | biostudies-literature
Project description:Renal carcinoma is a common and aggressive malignancy whose histopathogenesis is incompletely understood and that is largely resistant to cytotoxic chemotherapy. We present two mouse models of kidney cancer that recapitulate the genomic alterations found in human papillary (pRCC) and clear cell RCC (ccRCC), the most common RCC subtypes. MYC activation results in highly penetrant pRCC tumours (MYC), while MYC activation, when combined with Vhl and Cdkn2a (Ink4a/Arf) deletion (VIM), produce kidney tumours that approximate human ccRCC. RNAseq of the mouse tumours demonstrate that MYC tumours resemble Type 2 pRCC, which are known to harbour MYC activation. Furthermore, VIM tumours more closely simulate human ccRCC. Based on their high penetrance, short latency, and histologic fidelity, these models of papillary and clear cell RCC should be significant contributions to the field of kidney cancer research.
| S-EPMC5472759 | biostudies-literature
Project description:Metabolic reprogramming is critical during clear cell renal cell carcinoma (ccRCC) tumorigenesis, manifested by accumulation of lipid droplets (LDs), organelles that have emerged as new hallmarks of cancer. Yet, regulation of their biogenesis is still poorly understood. Here, we demonstrate that MYC inhibition in ccRCC cells lacking the von Hippel Lindau (VHL) gene leads to increased triglyceride content potentiating LD formation in a glutamine-dependent manner. Importantly, the concurrent inhibition of MYC signaling and glutamine metabolism prevented LD accumulation and reduced tumor burden in vivo. Furthermore, we identified the hypoxia-inducible lipid droplet-associated protein (HILPDA) as the key driver for induction of MYC-driven LD accumulation and demonstrated that conversely, proliferation, LD formation, and tumor growth are impaired upon its downregulation. Finally, analysis of ccRCC tissue as well as healthy renal control samples postulated HILPDA as a specific ccRCC biomarker. Together, these results provide an attractive approach for development of alternative therapeutic interventions for the treatment of this type of renal cancer.
| S-EPMC10873620 | biostudies-literature
Project description:Background: Clear cell renal cell carcinoma (ccRCC) is characterized by high metastatic potential, and the epithelial-mesenchymal transition (EMT) has been shown to play a key role in multiple cancer progression, migration and metastasis and is the leading cause of poor prognosis. Currently, tumor necrosis factor-α-induced protein 8 (TNFAIP8/TIPE) is a newly discovered tumorigenesis factor, and TNFAIP8 and the EMT influence the migration of renal cancer cells. Methods: In this study, we first analyzed the relationship between TNFAIP8 and ccRCC using bioinformatics, followed by immunohistochemistry to evaluate the relationship between the two in clinical samples. Subsequently, reverse transcription PCR and western blotting confirmed the expression of TNFAIP8 in ccRCC cells. Furthermore, we measured the migration and invasion abilities by using wound healing and transwell assays after overexpression or knockdown of TNFAIP8 in cells. In addition, we verified whether TNFAIP8 affects the EMT process in ccRCC by quantitative real-time PCR, western blotting, immunohistochemistry and immunofluorescence experiments. Results: Through database analysis, we found that TNFAIP8 was highly expressed in ccRCC patients and was positively correlated with tumor stage and grade, indicating that TNFAIP8 is associated with the development of advanced ccRCC and poor prognosis. We subsequently confirmed that TNFAIP8 was abnormally overexpressed in clinical samples and ccRCC cell lines and that TNFAIP8 promoted ccRCC cell migration and invasion in vitro. Finally, we found that TNFAIP8 regulated EMT-related molecule expression and regulated the EMT process. Conclusion: High expression of TNFAIP8 reinforces migration and regulates the EMT in ccRCC, conferring the metastatic potential of ccRCC and suggesting that TNFAIP8 may be a potential therapeutic target for the treatment of advanced ccRCC.
| S-EPMC7086265 | biostudies-literature
Project description:The von Hippel-Lindau (VHL) is deficient in ∼70% of clear-cell renal cell carcinomas (ccRCC), which contributes to the carcinogenesis and drug resistance of ccRCC. Here we show that VHL-deficient ccRCC cells present enhanced cytotoxicity of anthracyclines in a hypoxia-inducible factor-independent manner. By subtractive proteomic analysis coupling with RNAi or overexpression verification, aldehyde dehydrogenase 2 (ALDH2) is found to be transcriptionally regulated by VHL and contributes to enhanced anthracyclines cytotoxicity in ccRCC cells. Furthermore, VHL regulates ALDH2 expression by directly binding the promoter of -130 bp to -160 bp to activate the transcription of hepatocyte nuclear factor 4 alpha (HNF-4α). In addition, a positive correlation is found among the protein expressions of VHL, HNF-4α and ALDH2 in ccRCC samples. These findings will deepen our understanding of VHL function and shed light on precise treatment for ccRCC patients.
| S-EPMC5481740 | biostudies-literature