GENT-24. LONG NON-CODING RNA CRNDE AS A POTENTIAL EGFR-REGULATED ONCOGENE IN GLIOMA

Abstract

Long non-coding RNAs (lncRNAs) have recently been shown to play important roles in glioma development and progression. However, information on their functions and molecular mechanisms remains limited. Colorectal Neoplasia Differentially Expressed (CRNDE) is a novel lncRNA that has been found to be significantly upregulated in gliomas relative to normal brain tissues, and positively correlated with tumor grading. In the present study, we investigated the prognostic value of CRNDE and its underlying molecular mechanism in glioma. Based on two independent publicly accessible cohorts of glioblastoma multiforme patients treated with an uniform regimen, high CRNDE level was found to be associated with significantly poorer overall survival. Functional assays using three glioblastoma cell lines revealed that CRNDE knock-down could significantly inhibit glioma cell growth, increase cell apoptosis, induce cell cycle arrest at G0/G1 phase, and impair cell invasion. Further in vivo studies using a subcutaneous xenograft rodent model showed that cells with downregulated CRNDE expression exhibited significantly slower growth rate. We also identified a significant association between CRNDE expression and EGFR signaling in vitro. CRNDE expression was more abundant in EGFR-mutant samples than in EGFR-wild cases. Activation of EGFR signaling by EGF or inhibition by an EGFR-tyrosine kinase inhibitor in cell lines would enhance or suppress CRNDE expression, respectively. These findings suggest that CRNDE may potentially be under positive regulation by EGFR signaling, and may play a significant oncogenic role in glioma pathogenesis. CRNDE should be further explored as a potential biomarker and therapeutic target in glioma.