BACKGROUND: The long non-coding RNA CRNDE has emerged as an important regulator in carcinogenesis and cancer progression. While CRNDE has previously been found to be the most highly upregulated lncRNA in glioma, detailed information on its roles in regulating cancer cell growth remains limited. OBJECTIVE: In the present study, we aimed at exploring the functional roles and underlying mechanisms of CRNDE in glioma. METHODS: We applied microarray data analysis to determine the prognostic significance of CRNDE in glioma patients and its correlation with epidermal growth factor receptor (EGFR) activation. EGFR inhibition was used to confirm the role of EGFR in regulating CRNDE expression. Functional studies were performed upon CRNDE silencing to explore its role in gliomagenesis. RESULTS: We confirm that CRNDE acts as an oncogene that is highly up-regulated in glioma, and high CRNDE expression correlates with poor prognosis in glioma patients. We further demonstrate that the expression of CRNDE correlates with EGFR activation. EGF and EGFR tyrosine kinase inhibitor (TKI) enhance and block the up-regulation of CRNDE expression, respectively, suggesting that EGFR signaling may positively regulate CRNDE expression. Functional assays show that CRNDE depletion inhibits glioma cell growth both in vitro and in vivo, and is associated with induced cellular apoptosis with decreased Bcl2/Bax ratio. CONCLUSIONS: Our findings suggest that the aberrant expression of CRNDE may be mediated by activated EGFR signaling and play significant roles in gliomagenesis.
BACKGROUND: The long non-coding RNA CRNDE has emerged as an important regulator in carcinogenesis and cancer progression. While CRNDE has previously been found to be the most highly upregulated lncRNA in glioma, detailed information on its roles in regulating cancer cell growth remains limited. OBJECTIVE: In the present study, we aimed at exploring the functional roles and underlying mechanisms of CRNDE in glioma. METHODS: We applied microarray data analysis to determine the prognostic significance of CRNDE in gliomapatients and its correlation with epidermal growth factor receptor (EGFR) activation. EGFR inhibition was used to confirm the role of EGFR in regulating CRNDE expression. Functional studies were performed upon CRNDE silencing to explore its role in gliomagenesis. RESULTS: We confirm that CRNDE acts as an oncogene that is highly up-regulated in glioma, and high CRNDE expression correlates with poor prognosis in gliomapatients. We further demonstrate that the expression of CRNDE correlates with EGFR activation. EGF and EGFR tyrosine kinase inhibitor (TKI) enhance and block the up-regulation of CRNDE expression, respectively, suggesting that EGFR signaling may positively regulate CRNDE expression. Functional assays show that CRNDE depletion inhibits glioma cell growth both in vitro and in vivo, and is associated with induced cellular apoptosis with decreased Bcl2/Bax ratio. CONCLUSIONS: Our findings suggest that the aberrant expression of CRNDE may be mediated by activated EGFR signaling and play significant roles in gliomagenesis.
Authors: Gabriela D A Guardia; Bruna R Correa; Patricia Rosa Araujo; Mei Qiao; Suzanne Burns; Luiz O F Penalva; Pedro A F Galante Journal: NPJ Genom Med Date: 2020-01-16 Impact factor: 8.617