Oncogenic effects of evolutionarily conserved noncoding RNA ECONEXIN on gliomagenesis

Abstract

Accumulating studies have demonstrated the importance of long noncoding RNAs (lncRNAs) during oncogenic transformation. However, because most lncRNAs are currently uncharacterized, the identification of novel oncogenic lncRNAs is difficult. Given that intergenic lncRNA have substantially less sequence conservation patterns than protein-coding genes across species, evolutionary conserved intergenic lncRNAs are likely to be functional. The current study identified a novel intergenic lncRNA, LINC00461 (ECONEXIN) using a combined approach consisting of searching lncRNAs by evolutionary conservation and validating their expression in a glioma mouse model. ECONEXIN was the most highly conserved intergenic lncRNA containing 83.0% homology with the mouse ortholog (C130071C03Rik) for a region over 2500 bp in length within its exon 3. Expressions of ECONEXIN and C130071C03Rik were significantly upregulated in both human and mouse glioma tissues. Moreover, the expression of C130071C03Rik was upregulated even in precancerous conditions and markedly increased during glioma progression. Functional analysis of ECONEXIN in glioma cell lines, U87 and U251, showed it was dominantly located in the cytoplasm and interacted with miR-411-5p via two binding sites within ECONEXIN. Inhibition of ECONEXIN upregulated miR-411-5p together with the downregulation of its target, Topoisomerase 2 alpha (TOP2A), in glioma cell lines, resulting in decreased cell proliferation. Our data demonstrated that ECONEXIN is a potential oncogene that regulates TOP2A by sponging miR-411-5p in glioma. In addition, our investigative approaches to identify conserved lncRNA and their molecular characterization by validation in mouse tumor models may be useful to functionally annotate novel lncRNAs, especially cancer-associated lncRNAs.

LncRNA Riken‐201 and Riken‐203 modulates neural development by regulating the Sox6 through sequestering miRNAs

“…29 We also found that most of Rik-201, and part of Rik-203, are located in the cytoplasm (Figure 2A target in previous study 42 ( Figure S2B). 29 We also found that most of Rik-201, and part of Rik-203, are located in the cytoplasm (Figure 2A target in previous study 42 ( Figure S2B).…”

“…A recent study identified the novel Rik-201 and its homologous gene ECONEXIN and demonstrated its ceRNA functional role in gliomagenesis. 29 We also found that most of Rik-201, and part of Rik-203, are located in the cytoplasm (Figure 2A), which suggest they might function as the ceRNA. RNA pull-down experiments determined that miR-96 combined with Rik-201 ( Figure 2B), and miR-467a-3p combined with Rik-203 ( Figure 2C).…”

“…26,27 LncRNA ND regulates expression of Notch genes by sequestering miR-143-3p. 28 A recent study identified the novel Rik-201 and its homologous gene ECONEXIN, 29 and demonstrated its ceRNA functional role in gliomagenesis. 28 A recent study identified the novel Rik-201 and its homologous gene ECONEXIN, 29 and demonstrated its ceRNA functional role in gliomagenesis.…”

Sevoflurane regulating LncRNA Rik-203 contributes to neural differentiation via microRNA-466l-3p /BDNF pathway

“…LncRNAs, e.g., NBAT-1 and Pnky, may regulate cell differentiation and development [ [20][21][22], reviewed in [23]]. LncRNA Rik-201 plays important role in gliomagenesis [24]. However, the role of LncRNAs on neural differentiation, the process where embryonic stem cells (ESCs) mature into specialized neural progenitor cells (NPCs), which is crucial for cognitive function, neural development and neurotoxicity [25], remains largely unknown.…”

Long noncoding RNA LINC00152 is a potential prognostic biomarker in patients with high‐grade glioma

“…Upregulation of lncRNA HOXA‐AS3 promotes tumor progression and predicts poor prognosis in glioma . A novel lncRNA ECONEXIN is a potential oncogene that regulates TOP2A by sponging miR‐411‐5p in glioma . LncRNA H19 regulates glioma angiogenesis and the biological behavior of glioma‐associated endothelial cells by inhibiting miR‐29a .…”