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Mol Cancer Ther. 2016 Dec;15(12):2977-2986. doi: 10.1158/1535-7163.MCT-16-0320. Epub 2016 Oct 26.

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

Author information

1
Department of Neurosurgery, Navy General Hospital, PLA. Beijing, 100048, China.
2
Department of Cancer Biology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.
3
Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN 37203, USA.
4
Department of Recombinant Drugs, National Institutes for Food and Drug Control, Beijing, 100050, China.
5
Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37212, USA.
6
Center for Precision Health, School of Biomedical University, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA.
#
Contributed equally

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, TNFα/NF-κB, 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.

PMID:
27784795
PMCID:
PMC5136321
DOI:
10.1158/1535-7163.MCT-16-0320
[Indexed for MEDLINE]
Free PMC Article

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