Long Non-Coding RNA H19 Promotes Glioma Cell Invasion by Deriving miR-675

Abstract

H19 RNA has been characterized as an oncogenic long non-coding RNA (lncRNA) in breast and colon cancer. However, the role and function of lncRNA H19 in glioma development remain unclear. In this study, we identified that H19/miR-675 signaling was critical for glioma progression. By analyzing glioma gene expression data sets, we found increased H19 in high grade gliomas. H19 depletion via siRNA inhibited invasion in glioma cells. Further, we found H19 positively correlated with its derivate miR-675 expression and reduction of H19 inhibited miR-675 expression. Bioinformatics and luciferase reporter assays showed that miR-675 modulated Cadherin 13 expression by directly targeting the binding site within the 3′ UTR. Finally, introduction of miR-675 abrogated H19 knockdown-induced cell invasion inhibition in glioma cells. To our knowledge, it is first time to demonstrate that H19 regulates glioma development by deriving miR-675 and provide important clues for understanding the key roles of lncRNA-miRNA functional network in glioma.

The Bromodomain protein BRD4 controls HOTAIR, a long noncoding RNA essential for glioblastoma proliferation

“…Finally, H19 is one of most up-regulated lncRNAs in our RNAseq data, and it has been found to be overexpressed in glioma, where it promotes cell invasion (36). Here, we have shown that I-BET151 and BRD4 knockdown strongly reduce the expression of H19, confirming that functional noncoding RNAs should be taken into consideration when investigating the consequences of drug treatment on the gene expression profile of tumors.…”

“…S1A). Importantly, our analysis identified the previously characterized glioma-enriched lncRNA H19 (36), suggesting that our SMS pipeline robustly identifies lncRNAs overexpressed in glioma. Fig.…”

“…Given the emerging role of lncRNAs such as MEG3 (50), H19 (36), and HOTAIR (39) in regulating the cell cycle of GBM cells, our study uncovers an important connection between these lncRNAs and BET bromodomain proteins. Further, we identify a previously unidentified subset of genes regulated by the BET bromodomain inhibitors.…”

The role of micro-RNA in the regulation of signal pathways in gliomas

“…Анализ in vitro и in vivo моделей, при которых экспрессия miR-675-5p блокирована, демонстрирует, что при условии низкого содержания кислорода активность и синтез HIF1a в этом случае снижены, ответ на гипоксию, в том числе ангиогенез, не происходит [81]. MiR-675 модулирует экспрессию кадгерина 13 за счёт прямого связывания с его 3¢-UTR [82].…”

“…Введение miR-326 может являться новой стратегией терапии [35]. miR-326 ингибируется PI3-киназным каскадом [21] [ [20][21][22], [35], [37] miR-675-5p, ген которой находится внутри гена длинной некодирующей РНК Н19, играет роль в развитии ответа на гипоксию и гипоксия-опосредованном ангиогенезе [81] [81], [82] короткая длина зрелых микро-РНК ограничивает дизайн проб [101]. Несомненным преимуществом RNA-seq является возможность глубокого анализа дифференциальной экспрессии, в том числе поиска вариаций (SNP и др.…”