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Diffuse intrinsic pontine glioma (DIPG) is an incurable paediatric malignancy. Identifying the molecular drivers of DIPG progression is of the utmost importance. Long non-coding RNAs (lncRNAs) represent a large family of disease- and tissue-specific transcripts, whose functions have not yet been elucidated in DIPG. Herein, we studied the oncogenic role of the development-associated <i>H19</i> lncRNA in DIPG. Bioinformatic analyses of clinical datasets were used to measure the expression of <i>H19</i> lncRNA in paediatric high-grade gliomas (pedHGGs). The expression and sub-cellular location of <i>H19</i> lncRNA were validated in DIPG cell lines. Locked nucleic acid antisense oligonucleotides were designed to test the function of <i>H19</i> in DIPG cells. We found that <i>H19</i> expression was higher in DIPG vs. normal brain tissue and other pedHGGs. <i>H19</i> knockdown resulted in decreased cell proliferation and survival in DIPG cells. Mechanistically, <i>H19</i> buffers <i>let-7</i> microRNAs, resulting in the up-regulation of oncogenic <i>let-7</i> target (e.g., <i>SULF2</i> and <i>OSMR</i>). <i>H19</i> is the first functionally characterized lncRNA in DIPG and a promising therapeutic candidate for treating this incurable cancer.