Differential Expression of Circular RNAs in Glioblastoma Multiforme and Its Correlation with Prognosis

Zhu, Jing; Ye, Jingliang; Zhang, Lei; Xia, Lili; Hu, Haitao; Jiang, Heng; Wan, Zhang; Sheng, Fei; Ma, Yan; Li, Wen; Qian, Jun; Luo, Chun

doi:10.1016/j.tranon.2016.12.006

Cited by 91 publications

(79 citation statements)

References 32 publications

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“…The GSE63319 dataset included miRNA microarray data of 11 GBM tissues and four epileptic tissues and was based on GPL16384 Affymetrix Multispecies miRNA‐3 Array (Affymetrix, Inc, Santa Clara, CA) 8 . The GSE103227 dataset, which comprised gene expression microarray data and lncRNA microarray data, was based on GPL16956 Platforms (Agilent‐045997 Arraystar human lncRNA microarray V3 (Probe Name Version), Arraystar Inc, Rockville, MD) and included data from five GBM and five normal brain tissues 9 . The RNA‐seq data expression profiles of GBM were obtained from The Cancer Genome Atlas (TCGA) public database (http://cancergenome.nih.gov/) (as of December, 2018) using the Data Transfer Tool, which included data of 169 GBM and five non‐tumoral brain samples, for DEmRNA and DElncRNA analysis, and the clinical information of the cases was also collected.…”

Section: Experimental Methods and Designmentioning

confidence: 99%

Construction of lncRNA‐associated ceRNA networks to identify prognostic lncRNA biomarkers for glioblastoma

Liu

Wang

Yang

et al. 2020

J of Cellular Biochemistry

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Long noncoding RNAs (lncRNAs) serve as competitive endogenous RNAs (ceRNAs) that play significant regulatory roles in the pathogenesis of tumors. However, the role of lncRNAs, especially the lncRNA-related ceRNA regulatory network, in glioblastoma (GBM) has not been fully elucidated. The goal of the current study was to construct lncRNA-microRNA-mRNA-related ceRNA networks for further investigation of their mechanism of action in GBM. We downloaded data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases and identified differential lncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) associated with GBM. A ceRNA network was constructed and analyzed to examine the relationship between lncRNAs and patients' overall survival. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGGs) were used to analyze the related mRNAs to indirectly explain the mechanism of action of lncRNAs. The potential effective drugs for the treatment of GBM were identified using the connectivity map (CMap). After integrated analysis, we obtained a total of 210 differentially expressed lncRNAs, 90 differentially expressed miRNAs, and 2508 differentially expressed mRNAs (DEmRNAs) from the TCGA and GEO databases. Using these differential genes, we constructed a lncRNA-associated ceRNA network. Six lncRNAs in the ceRNA network were associated with the overall survival of patients with GBM. Through KEGG analysis, it was found that the DEmRNAs involved in the network are related to cancer-associated pathways, for instance, mitogen-activated protein kinase and Ras signaling pathways. CMap analysis revealed four small-molecule compounds that could be used as drugs for the treatment of GBM. In this study, a multi-database joint analysis was used to construct a lncRNA-related ceRNA network to help identify the regulatory functions of lncRNAs in the pathogenesis of GBM.

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Section: Experimental Methods and Designmentioning

confidence: 99%

Construction of lncRNA‐associated ceRNA networks to identify prognostic lncRNA biomarkers for glioblastoma

Liu

Wang

Yang

et al. 2020

J of Cellular Biochemistry

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“…CircRNAs are aberrantly expressed in several types of cancer, where they regulate multiple biological processes [115], including in brain tumors [116][117][118] (Table 2). For instance, circSMARCA5 was identified as one of the circRNAs most differentially expressed in a cohort of fifty-six GBM patient biopsies.…”

Section: Back Splicing In Brain Tumorsmentioning

confidence: 99%

Splicing Dysregulation as Oncogenic Driver and Passenger Factor in Brain Tumors

Bielli

Pagliarini

Pieraccioli

et al. 2019

Cells

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Brain tumors are a heterogeneous group of neoplasms ranging from almost benign to highly aggressive phenotypes. The malignancy of these tumors mostly relies on gene expression reprogramming, which is frequently accompanied by the aberrant regulation of RNA processing mechanisms. In brain tumors, defects in alternative splicing result either from the dysregulation of expression and activity of splicing factors, or from mutations in the genes encoding splicing machinery components. Aberrant splicing regulation can generate dysfunctional proteins that lead to modification of fundamental physiological cellular processes, thus contributing to the development or progression of brain tumors. Herein, we summarize the current knowledge on splicing abnormalities in brain tumors and how these alterations contribute to the disease by sustaining proliferative signaling, escaping growth suppressors, or establishing a tumor microenvironment that fosters angiogenesis and intercellular communications. Lastly, we review recent efforts aimed at developing novel splicing-targeted cancer therapies, which employ oligonucleotide-based approaches or chemical modulators of alternative splicing that elicit an impact on brain tumor biology.

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“…With advances in high‐throughput sequencing and bioinformatic analysis, accumulated evidence indicated that circRNAs were abundant in mammalian cells and even highly expressed compared with the linear RNA isoforms of the host genes . Recent evidence indicated that the aberrant expression profile of circRNAs occurs in colorectal cancer, bladder carcinoma, breast cancer, and glioblastoma . Therefore, circRNAs are important in the tumorigenesis of various kinds of cancers.…”

Section: Introductionmentioning

confidence: 99%

Dysregulated circular RNAs in medulloblastoma regulate proliferation and growth of tumor cells via host genes

Miao

et al. 2018

Cancer Medicine

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Circular RNAs (circRNAs) have been demonstrated to be involved in various biological processes. Nevertheless, the function of circRNAs in medulloblastoma (MB) is still unknown. The present study aimed to investigate the expression profiles of circRNAs and related mechanisms for regulating the proliferation and growth of tumor cells in MB. The expression profiles of circRNAs were screened from four normal cerebellum and four MB samples using a HiSeq Sequencer. Bioinformatic analysis was employed to predict the interaction between circRNAs and mRNAs in MB. Subsequently, the expression levels of eight differential circRNAs [circ‐SKA3 (hsa_circ_0029696), circ‐DTL (hsa_circ_0000179), circ‐CRTAM, circ‐MAP3K5 (hsa_circ_0006856), circ‐RIMS1‐1 (hsa_circ_0132250), circ‐RIMS1‐2 (hsa_circ_0076967), circ‐FLT3‐1 (hsa_circ_0100165), and circ‐FLT3‐2 (hsa_circ_0100168)] were validated using quantitative reverse transcription−polymerase chain reaction. Moreover, circ‐SKA3 and circ‐DTL were silenced using small interfering RNAs and their host genes were overexpressed to investigate their role in the pathogenesis of MB. A total of 33 circRNAs were found to be differentially expressed in MB tissues (fold change ≥ 2.0, FDR <0.05), of which three were upregulated and 30 were downregulated; six circRNAs were experimentally validated successfully. Upregulated circ‐SKA3 and circ‐DTL promoted the proliferation migration and invasion in vitro by regulating the expression of host genes. This novel study exploited the profiling of circRNAs in MB and demonstrated that circ‐SKA3 and circ‐DTL were crucial in the tumorigenesis and development of MB and might be considered as novel and potential biomarkers for the diagnosis and new targets for the intervention of MB.

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Differential Expression of Circular RNAs in Glioblastoma Multiforme and Its Correlation with Prognosis

Cited by 91 publications

References 32 publications

Construction of lncRNA‐associated ceRNA networks to identify prognostic lncRNA biomarkers for glioblastoma

Construction of lncRNA‐associated ceRNA networks to identify prognostic lncRNA biomarkers for glioblastoma

Splicing Dysregulation as Oncogenic Driver and Passenger Factor in Brain Tumors

Dysregulated circular RNAs in medulloblastoma regulate proliferation and growth of tumor cells via host genes

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