Dataset Information

Alternative polyadenylation in glioblastoma multiforme and changes in predicted RNA binding protein profiles.

ABSTRACT: Alternative polyadenylation (APA) is widely present in the human genome and plays a key role in carcinogenesis. We conducted a comprehensive analysis of the APA products in glioblastoma multiforme (GBM, one of the most lethal brain tumors) and normal brain tissues and further developed a computational pipeline, RNAelements (http://sysbio.zju.edu.cn/RNAelements/), using covariance model from known RNA binding protein (RBP) targets acquired by RNA Immunoprecipitation (RIP) analysis. We identified 4530 APA isoforms for 2733 genes in GBM, and found that 182 APA isoforms from 148 genes showed significant differential expression between normal and GBM brain tissues. We then focused on three genes with long and short APA isoforms that show inconsistent expression changes between normal and GBM brain tissues. These were myocyte enhancer factor 2D, heat shock factor binding protein 1, and polyhomeotic homolog 1 (Drosophila). Using the RNAelements program, we found that RBP binding sites were enriched in the alternative regions between the first and the last polyadenylation sites, which would result in the short APA forms escaping regulation from those RNA binding proteins. To the best of our knowledge, this report is the first comprehensive APA isoform dataset for GBM and normal brain tissues. Additionally, we demonstrated a putative novel APA-mediated mechanism for controlling RNA stability and translation for APA isoforms. These observations collectively lay a foundation for novel diagnostics and molecular mechanisms that can inform future therapeutic interventions for GBM.

SUBMITTER: Shao J

PROVIDER: S-EPMC3603499 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Alternative polyadenylation in glioblastoma multiforme and changes in predicted RNA binding protein profiles.

Shao Jiaofang J Zhang Jing J Zhang Zengming Z Jiang Huawei H Lou Xiaoyan X Huang Bingding B Foltz Gregory G Lan Qing Q Huang Qiang Q Lin Biaoyang B

Omics : a journal of integrative biology 20130219 3

Alternative polyadenylation (APA) is widely present in the human genome and plays a key role in carcinogenesis. We conducted a comprehensive analysis of the APA products in glioblastoma multiforme (GBM, one of the most lethal brain tumors) and normal brain tissues and further developed a computational pipeline, RNAelements (http://sysbio.zju.edu.cn/RNAelements/), using covariance model from known RNA binding protein (RBP) targets acquired by RNA Immunoprecipitation (RIP) analysis. We identified ...[more]

PMID: 23421905

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Project description:Purpose: Glioblastoma multiforme (GBM) is the most widely occurring brain malignancy. It is modulated by a variety of genes, and patients with GBM have a low survival ratio and an unsatisfactory treatment effect. The irregular regulation of RNA binding proteins (RBPs) is implicated in several malignant neoplasms and reported to exhibit an association with the occurrence and development of carcinoma. Thus, it is necessary to build a stable, multi-RBPs signature-originated model for GBM prognosis and treatment response prediction. Methods: Differentially expressed RBPs (DERBPs) were screened out based on the RBPs data of GBM and normal brain tissues from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Program (GTEx) datasets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses on DERBPs were performed, followed by an analysis of the Protein-Protein Interaction network. Survival analysis of the DERBPs was conducted by univariate and multivariate Cox regression. Then, a risk score model was created on the basis of the gene signatures in various survival-associated RBPs, and its prognostic and predictive values were evaluated through Kaplan-Meier analysis and log-rank test. A nomogram on the basis of the hub RBPs signature was applied to estimate GBM patients' survival rates. Moreover, western blot was for the detection of the proteins. Results: BICC1, GNL3L, and KHDRBS2 were considered as prognosis-associated hub RBPs and then were applied in the construction of a prognostic model. Poor survival results appeared in GBM patients with a high-risk score. The area under the time-dependent ROC curve of the prognostic model was 0.723 in TCGA and 0.707 in Chinese Glioma Genome Atlas (CGGA) cohorts, indicating a good prognostic model. What was more, the survival duration of the high-risk group receiving radiotherapy or temozolomide chemotherapy was shorter than that of the low-risk group. The nomogram showed a great discriminating capacity for GBM, and western blot experiments demonstrated that the proteins of these 3 RBPs had different expressions in GBM cells. Conclusion: The identified 3 hub RBPs-derived risk score is effective in the prediction of GBM prognosis and treatment response, and benefits to the treatment of GBM patients.

Dataset Information

Alternative polyadenylation in glioblastoma multiforme and changes in predicted RNA binding protein profiles.

Publications

Alternative polyadenylation in glioblastoma multiforme and changes in predicted RNA binding protein profiles.

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