Identification of KPNA2 targets by RNA-Seq in osteosarcoma
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA850355 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR19733721_1.fastq.gz | Fastqsanger.gz | |||
| SRR19733721_2.fastq.gz | Fastqsanger.gz | |||
| SRR19733722_1.fastq.gz | Fastqsanger.gz | |||
| SRR19733722_2.fastq.gz | Fastqsanger.gz | |||
| SRR19733723_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
Project description:Despite recent advances, the poor outcomes in osteosarcoma suggest that novel therapeutic targets are needed. Karyopherin alpha 2 (KPNA2) is a nuclear import factor, which functions as an oncogene in many cancers. However, the role of KPNA2 in osteosarcoma and its mechanism of action are still unclear. To identify gene signatures that play a role in metastasis, we performed RNA-Seq of gene expression profiling on U2OS cells treated with siKPNA2 and siNC (in triplicate for each group).
2023-06-16 | GSE206342 | GEO
Project description:Osteosarcoma (OS) is a rapidly progressive primary malignant bone tumor that usually occurs in adolescents between 15 and 19 years old and adults over 60 years old. Over the past 20 years, limited progress has been made in neoadjuvant chemotherapy and surgery aimed at curing OS. It is well known that alternative splicing (AS) changes caused by abnormal splicing factors contribute to tumor progression. But at present, there is a lack of extensive and in-depth AS research on OS. Gene expression analysis and AS analysis were performed on the sequencing data of 44 patients with osteosarcoma in order to construct a co-expression network among RNA-binding proteins, AS events, and AS genes in the whole genome. The gain or loss of functional osteosarcoma cell model was made, and the osteosarcoma phenotype was proved by in vitro and in vivo experiments. Interactive network analysis and enrichment analysis were carried out to define the internal mechanism.We screened the RBP of Karyopherin Subunit Alpha 2 (KPNA2), which was highly expressed in osteosarcoma cells and negatively correlated with patient survival. KPNA2 transports splicing factor Y-box Binding Protein 1 (YBX1) into the nucleus and promotes the proliferation, migration, and invasion of osteosarcoma. Using RNA-seq, we comprehensively screened and identified multiple AS events affected by YBX1. Specifically, YBX1 accelerates the degradation of ATP-dependent RNA helicase DDX3X (DDX3X) through the Nonsense-mediated decay (NMD) pathway by promoting the intron retention of the DDX3X gene, thus reducing the level of DDX3X protein. The changes in DDX3X in OS will affect significant changes in cell cycle-related proteins, including p53, p21, and AKT1. The KPNA2/YBX1 axis can regulate the stability of DDX3X mRNA and then affect the progress of the cell cycle. YBX1 promotes the proliferation, migration, and invasion of osteosarcoma by regulating the AS event of DDX3X. KPNA2/YBX1 axis activation is an important factor driving abnormal AS in OS. Importantly, we demonstrated that therapeutic targeting of the KPNA2/YBX1/DDX3X axis can inhibit OS proliferation and disease progression. It integrates the AS control of DDX3X into the progression of OS and represents potential prognostic biomarkers and targets of OS therapy.
2025-07-02 | GSE263410 | GEO
Project description:Identification of ALKBH5 targets in osteosarcoma by methyl RNA immunoprecipitation [MeRIP-seq]
| PRJNA646541 | ENA
Project description:RNA binding proteins (RBPs) took a critical part in genome regulation. kpna2, as an essential member of the RBP family, was found to be highly expressed and associated with lymph node metastasis in gastric cancer (GC). Transcriptional sequencing data were used to find that KPNA2 primarily regulated alternative 5' splice site (A5SS), alternative 3'splice site (A3SS), exon skipping (ES) and cassette exon. Vitally, KPNA2 was involved in the transcriptional regulation of cancer-related genes. Therefore, we screened potential targets in AGS cells with differential expression and alternative splicing (AS) levels regulated by KPNA2, further identifying that KPNA2 was engaged in biological processes concerning immune response, cell proliferation and apoptosis in GC through transcriptional regulation. Besides, the binding sites of KPNA2 to spliceosomes were identified using improved RNA immunoprecipitation sequencing techniques, and KPNA2 was preferentially bound to the intron region. Notably, KPNA2 regulated the A3SS AS mode of WDR62, which may increase the malignancy of GC. Finally, we also discovered that AS of immune-related molecules can be regulated by KPNA2. Overall, for the first time, our results demonstrated that KPNA2 served as an oncogenic splicing factor in GC regulating AS and differential expression of GC-related genes and may represent a potential target for GC therap
2024-08-02 | GSE201418 | GEO
Project description:RNA binding proteins (RBPs) took a critical part in genome regulation. kpna2, as an essential member of the RBP family, was found to be highly expressed and associated with lymph node metastasis in gastric cancer (GC). Transcriptional sequencing data were used to find that KPNA2 primarily regulated alternative 5' splice site (A5SS), alternative 3'splice site (A3SS), exon skipping (ES) and cassette exon. Vitally, KPNA2 was involved in the transcriptional regulation of cancer-related genes. Therefore, we screened potential targets in AGS cells with differential expression and alternative splicing (AS) levels regulated by KPNA2, further identifying that KPNA2 was engaged in biological processes concerning immune response, cell proliferation and apoptosis in GC through transcriptional regulation. Besides, the binding sites of KPNA2 to spliceosomes were identified using improved RNA immunoprecipitation sequencing techniques, and KPNA2 was preferentially bound to the intron region. Notably, KPNA2 regulated the A3SS AS mode of WDR62, which may increase the malignancy of GC. Finally, we also discovered that AS of immune-related molecules can be regulated by KPNA2. Overall, for the first time, our results demonstrated that KPNA2 served as an oncogenic splicing factor in GC regulating AS and differential expression of GC-related genes and may represent a potential target for GC therap
2024-08-02 | GSE201419 | GEO
Project description:Karyopherin α 2 (KPNA2, importin α1) is involved in the nuclear import of proteins and participates in cellular processes and accumulates in the nucleus under cellular stresses including hydrogen peroxide-indeced oxidative stress via unknown mechanisms. We performed the immunoprecipitation assay and SILAC-based quantitative proteomic analysis in HeLa cells to reveal that hydrogen peroxide decreased the phosphorylation of KPNA2 at serine 62 (S62) and increased its interaction with nucleophosmin 1 (NPM1). Specifically, a reduction in phosphorylated S62 on KPNA2 was observed in the cytoplasmic fraction, but this phosphorylated KPNA2 was not detected in the nuclear fraction. We also identified fifty-four KPNA2-interacting proteins in the nuclear fraction. Among them, NPM1, RPLP0, and MYH9 interacted with KPNA2 in cells exposed to hydrogen peroxide but not in unstressed control cells. Furthermore, the subcellular fractionation, immunoprecipitation, western blotting, immunofluorescence assay, and qRT-PCR analyses were used to support a novel finding that S62 phosphorylation maintains KPNA2 in the cytoplasm, and hydrogen peroxide reduces the phosphorylation of KPNA2 S62 to promote KPNA2-NPM1 complex nuclear entry for gene regulation.
2024-10-17 | PXD051121 | Pride
Project description:KPNA2 promotes osteosarcoma by regulating the alternative splicing of DDX3X mediated by YBX1
| PRJNA1097489 | ENA
Project description:To identify potential target mRNAs that are demethylated by ALKBH5, meRIP-seq with a m6A antibody was conducted in 143B osteosarcoma cells transfected with scrambled or ALKBH5-siRNA.
2022-06-28 | GSE154529 | GEO
Project description:Despite the development of diagnostic and advanced treatment strategies, the prognosis of patients with osteosarcoma remains poor. A limited understanding of the pathogenesis of osteosarcomas has impeded any improvement in patient outcomes over the past 4 decades. It is thus urgent to identify novel effective targets and treatment regimens for osteosarcoma patients. In this study we delineated the super-enhancer landscape in osteosarcoma cells on the basis of H3K27ac signal intensity by ChIP-Seq and found that super-enhancer-associated genes contribute to the malignant potential of osteosarcoma. THZ2, a novel small molecular inhibitor, shows a powerful anti-osteosarcoma ability through suppress super-enhancer-associated genes selectively. Utilizing the characteristics of super-enhancers in cancer cells, we identified 5 critical super-enhancer-associated oncogenes. With the comparative and retrospective analysis in large numbers of human specimens from patients, these 5 oncogenes were observed closely related with patient prognosis. Our findings determined that targeting super-enhancer-associated oncogenes with transcriptional inhibitor, THZ2, was a promising therapeutic strategy in osteosarcoma, and provided novel candidate targets for patients with osteosarcoma.
2019-12-27 | GSE134604 | GEO
Project description:Identification of RoxS targets
| PRJNA954386 | ENA