BACKGROUND

While RNA-binding proteins (RBPs) are known to affect RNA homeostasis during cancer cell initiation and development, their characteristics and biological function in glioblastoma (GBM) remain unclear.

METHODS

Differences in RBP expression were explored by differential analysis of The Cancer Genome Atlas-GBM and Genotype-Tissue Expression (GTEx) datasets. Real-time PCR was conducted to verify the expressional levels of Aly/REF export factor () in normal brain and GBM tissues. Proliferative assays were performed to investigate molecular functions of in GBM cells in vitro and in vivo. Real-time PCR and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed to analyze the downstream signaling pathways. A chromatin immunoprecipitation (ChIP) assay was performed to identify key transcriptional factors that regulate expression at RNA level. UV crosslinking, immunoprecipitation (CLIP) and RNA stability assays were conducted to reveal the bound RNAs and their stability regulated by .

RESULTS

The results showed that is frequently increased in GBM tissues, and its mRNA expression is regulated by the MYC proto-oncogene, bHLH transcription factor (). Inhibition of expression decreased GBM cell proliferative ability in vitro and tumor formation in vivo. KEGG analysis revealed that high expression in GBM tissues was enriched in the upregulation of oncogenic pathways such as the Wnt/β-catenin signaling pathway. The CLIP assay showed that drives GBM carcinogenesis by binding to and stabilizing mRNAs. Overexpression of restored the oncogenic property of -deficient GBM cells.

CONCLUSION

Our data showed that is regulated by at the transcriptional level. drives GBM cell proliferation by activating the Wnt/β-catenin signaling pathway and stabilizing mRNA, suggesting that an positive feedback loop might be a potential therapeutic target for treating GBM patients.