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CRNDE Expression Positively Correlates with EGFR Activation and Modulates Glioma Cell Growth

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Abstract

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.

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Author notes

  1. Karrie Mei-Yee Kiang and Xiao-Qin Zhang contributed equally to this work.

Authors and Affiliations

  1. Division of Neurosurgery, Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong, Hong Kong

    Karrie Mei-Yee Kiang, Xiao-Qin Zhang, Grace Pingde Zhang, Ning Li, Stephen Yin Cheng, Ming-Wai Poon, Jenny Kan-Suen Pu, Wai-Man Lui & Gilberto Ka-Kit Leung

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  1. Karrie Mei-Yee Kiang
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Correspondence to Gilberto Ka-Kit Leung.

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Kiang, K.MY., Zhang, XQ., Zhang, G.P. et al. CRNDE Expression Positively Correlates with EGFR Activation and Modulates Glioma Cell Growth. Targ Oncol 12, 353–363 (2017). https://doi.org/10.1007/s11523-017-0488-3

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