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Mol Cancer Res. 2018 Oct;16(10):1470-1482. doi: 10.1158/1541-7786.MCR-18-0322. Epub 2018 Jul 10.

LINC00152 Promotes Invasion through a 3'-Hairpin Structure and Associates with Prognosis in Glioblastoma.

Author information

1
Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia.
2
Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia. ad8q@virginia.edu.
#
Contributed equally

Abstract

Long noncoding RNAs (lncRNA) are increasingly implicated in oncogenesis. Here, it is determined that LINC00152/CYTOR is upregulated in glioblastoma multiforme (GBM) and aggressive wild-type IDH1/2 grade 2/3 gliomas and upregulation associates with poor patient outcomes. LINC00152 is similarly upregulated in over 10 other cancer types and associates with a poor prognosis in 7 other cancer types. Inhibition of the mostly cytoplasmic LINC00152 decreases, and overexpression increases cellular invasion. LINC00152 knockdown alters the transcription of genes important to epithelial-to-mesenchymal transition (EMT). PARIS and Ribo-seq data, together with secondary structure prediction, identified a protein-bound 121-bp stem-loop structure at the 3' end of LINC00152 whose overexpression is sufficient to increase invasion of GBM cells. Point mutations in the stem-loop suggest that stem formation in the hairpin is essential for LINC00152 function. LINC00152 has a nearly identical homolog, MIR4435-2HG, which encodes a near identical hairpin, is equally expressed in low-grade glioma (LGG) and GBM, predicts poor patient survival in these tumors, and is also reduced by LINC00152 knockdown. Together, these data reveal that LINC00152 and its homolog MIR4435-2HG associate with aggressive tumors and promote cellular invasion through a mechanism that requires the structural integrity of a hairpin structure.Implications: Frequent upregulation of the lncRNA, LINC00152, in glioblastoma and other tumor types combined with its prognostic potential and ability to promote invasion suggests LINC00152 as a potential biomarker and therapeutic target. Mol Cancer Res; 16(10); 1470-82. ©2018 AACR.

PMID:
29991527
PMCID:
PMC6170721
[Available on 2019-10-01]
DOI:
10.1158/1541-7786.MCR-18-0322

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