Dataset Information

The Potential Roles of Long Noncoding RNAs (lncRNA) in Glioblastoma Development.

ABSTRACT: Long noncoding RNA (lncRNA) may contribute to the initiation and progression of tumor. In this study, we first systematically compared lncRNA and mRNA expression between glioblastoma and paired normal brain tissues using microarray data. We found 27 lncRNA and 82 mRNA significantly upregulated in glioblastoma, as well as 198 lncRNA and 285 mRNA significantly downregulated in glioblastoma. We identified 138 coexpressed lncRNA-mRNA pairs from these differentially expressed lncRNA and genes. Subsequent pathway analysis of the lncRNA-paired genes indicated that EphrinB-EPHB, p75-mediated signaling, TNF?/NF-?B, and ErbB2/ErbB3 signaling pathways might be altered in glioblastoma. Specifically, lncRNA RAMP2-AS1 had significant decrease of expression in glioblastoma tissues and showed coexpressional relationship with NOTCH3, an important tumor promoter in many neoplastic diseases. Our follow up experiment indicated that (i) an overexpression of RAMP2-AS1 reduced glioblastoma cell proliferation in vitro and also reduced glioblastoma xenograft tumors in vivo; (ii) NOTCH3 and RAMP2-AS1 coexpression rescued the inhibitory action of RAMP2-AS1 in glioblastoma cells; and (iii) RNA pull-down assay revealed a direct interaction of RAMP2-AS1 with DHC10, which may consequently inhibit, as we hypothesize, the expression of NOTCH3 and its downstream signaling molecule HES1 in glioblastoma. Taken together, our data revealed that lncRNA expression profile in glioblastoma tissue was significantly altered; and RAMP2-AS1 might play a tumor suppressive role in glioblastoma through an indirect inhibition of NOTCH3 Our results provided some insights into understanding the key roles of lncRNA-mRNA coregulation in human glioblastoma and the mechanisms responsible for glioblastoma progression and pathogenesis. Mol Cancer Ther; 15(12); 2977-86. ©2016 AACR.

SUBMITTER: Liu S

PROVIDER: S-EPMC5136321 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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The Potential Roles of Long Noncoding RNAs (lncRNA) in Glioblastoma Development.

Liu Shuang S Mitra Ramkrishna R Zhao Ming-Ming MM Fan Wenhong W Eischen Christine M CM Yin Feng F Zhao Zhongming Z

Molecular cancer therapeutics 20161026 12

Long noncoding RNA (lncRNA) may contribute to the initiation and progression of tumor. In this study, we first systematically compared lncRNA and mRNA expression between glioblastoma and paired normal brain tissues using microarray data. We found 27 lncRNA and 82 mRNA significantly upregulated in glioblastoma, as well as 198 lncRNA and 285 mRNA significantly downregulated in glioblastoma. We identified 138 coexpressed lncRNA-mRNA pairs from these differentially expressed lncRNA and genes. Subseq ...[more]

PMID: 27784795

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Project description:AimsAnthracyclines (ANTs) are essential chemotherapeutic agents; however, their adverse effects can lead to heart failure in cancer survivors. While long non-coding RNAs (lncRNAs) have become new players in cellular processes, there is limited knowledge on lncRNA expression related to anthracyclines-induced cardiotoxicity. This study investigates the lncRNA profiles in human cardiac microtissues exposed to 3 popular ANTs, namely doxorubicin, epirubicin, and idarubicin, as well as in heart biopsies from ANT-treated patients.Methods and resultsThe in vitro microtissues were exposed to each ANT at 2 doses over 2 weeks; the transcriptome data was collected at 7 time points. The human biopsies were collected from heart failure patients who underwent ANT treatment and control subjects. Over 100 lncRNAs were differentially expressed in each in vitro ANT treatment condition compared to control samples; 16 of them were differentially expressed across all ANT-treated conditions. The lncRNA databases and literature revealed insight on how these lncRNAs relate to heart failure and cellular functions. For instance, H19 and RMRP are involved in heart failure progression, while BDNF-AS is a cardiomyocyte damage-associated gene; SNHG7 is a cardiac hypertrophy regulator. PCAT19 can promote the miR-182/PDK4 axis and modulate p53 expression, whereas SNHG29 can regulate the Wnt/β-catenin signaling pathway via the miR-223-3p/CTNND1 axis. Other lncRNAs, which were only differentially expressed in particular ANT-treated conditions, are also involved in cardiomyocyte damage and heart failure disease. The alterations of these lncRNA expressions in the in vitro cardiac tissue were also affirmed by similar changes in the human biopsies.ConclusionThis study revealed several lncRNAs that can be potential biomarkers or targets for further ANT-induced cardiotoxicity investigation, according to the transcriptome in both human cardiac microtissues expose to ANTs as well as in heart biopies form ANT-treated patients. Especially, H19 lncRNA showed its contribution to on-target toxicity, in which it is involved in both chemoresistance and cardiotoxic mechanism.

Dataset Information

The Potential Roles of Long Noncoding RNAs (lncRNA) in Glioblastoma Development.

Publications

The Potential Roles of Long Noncoding RNAs (lncRNA) in Glioblastoma Development.

Similar Datasets

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